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Gene Information

Gene symbol: CD40

Gene name: CD40 molecule, TNF receptor superfamily member 5

HGNC ID: 11919

Synonyms: p50, Bp50

Related Genes

# Gene Symbol Number of hits
1 AAVS1 1 hits
2 ACPP 1 hits
3 AD5 1 hits
4 ADAM11 1 hits
5 ADAM17 1 hits
6 ADCY10 1 hits
7 AICDA 1 hits
8 AKT1 1 hits
9 APC 1 hits
10 APP 1 hits
11 BCL2 1 hits
12 BCL6 1 hits
13 BCR 1 hits
14 BTLA 1 hits
15 C19orf10 1 hits
16 C8orf4 1 hits
17 CAMLG 1 hits
18 CASP8 1 hits
19 CAV1 1 hits
20 CBL 1 hits
21 CCDC91 1 hits
22 CCL17 1 hits
23 CCL18 1 hits
24 CCL19 1 hits
25 CCL2 1 hits
26 CCL21 1 hits
27 CCL27 1 hits
28 CCL3 1 hits
29 CCL4 1 hits
30 CCL5 1 hits
31 CCND1 1 hits
32 CCR2 1 hits
33 CCR5 1 hits
34 CCR6 1 hits
35 CCR7 1 hits
36 CCRN4L 1 hits
37 CD14 1 hits
38 CD19 1 hits
39 CD1A 1 hits
40 CD1B 1 hits
41 CD1C 1 hits
42 CD1D 1 hits
43 CD209 1 hits
44 CD22 1 hits
45 CD27 1 hits
46 CD274 1 hits
47 CD28 1 hits
48 CD34 1 hits
49 CD36 1 hits
50 CD38 1 hits
51 CD4 1 hits
52 CD40LG 1 hits
53 CD5 1 hits
54 CD58 1 hits
55 CD59 1 hits
56 CD68 1 hits
57 CD69 1 hits
58 CD70 1 hits
59 CD79A 1 hits
60 CD80 1 hits
61 CD83 1 hits
62 CD86 1 hits
63 CD8A 1 hits
64 CEACAM5 1 hits
65 CELIAC3 1 hits
66 CLEC11A 1 hits
67 CLEC4D 1 hits
68 CLEC9A 1 hits
69 COL1A1 1 hits
70 COL2A1 1 hits
71 CPAT1 1 hits
72 CR2 1 hits
73 CREB1 1 hits
74 CRP 1 hits
75 CSF1 1 hits
76 CSF2 1 hits
77 CTLA4 1 hits
78 CTS1 1 hits
79 CXCL10 1 hits
80 CXCL2 1 hits
81 CXCR3 1 hits
82 CXCR4 1 hits
83 CYP1B1 1 hits
84 DTYMK 1 hits
85 DUSP11 1 hits
86 EBNA1BP2 1 hits
87 EIF2AK2 1 hits
88 ERBB2 1 hits
89 FADD 1 hits
90 FAS 1 hits
91 FASLG 1 hits
92 FCER2 1 hits
93 FCGR2A 1 hits
94 FCGR3A 1 hits
95 FKBP1A 1 hits
96 FLT3 1 hits
97 FOS 1 hits
98 FOXP3 1 hits
99 GALT 1 hits
100 GINS2 1 hits
101 GLI2 1 hits
102 GORASP1 1 hits
103 GP5 1 hits
104 GPI 1 hits
105 GZMB 1 hits
106 HLA-A 1 hits
107 HLA-B 1 hits
108 HOXD13 1 hits
109 HSP90AA1 1 hits
110 HSPA1A 1 hits
111 HSPD1 1 hits
112 ICAM1 1 hits
113 ICAM3 1 hits
114 ICOS 1 hits
115 IFIH1 1 hits
116 IFN1 1 hits
117 IFNA1 1 hits
118 IFNB1 1 hits
119 IFNG 1 hits
120 IL10 1 hits
121 IL12A 1 hits
122 IL12B 1 hits
123 IL13 1 hits
124 IL15 1 hits
125 IL17A 1 hits
126 IL17C 1 hits
127 IL18 1 hits
128 IL1A 1 hits
129 IL1B 1 hits
130 IL1R1 1 hits
131 IL2 1 hits
132 IL27 1 hits
133 IL2RA 1 hits
134 IL3 1 hits
135 IL3RA 1 hits
136 IL4 1 hits
137 IL5 1 hits
138 IL6 1 hits
139 IL7 1 hits
140 IL8 1 hits
141 IL9 1 hits
142 INDO 1 hits
143 INS 1 hits
144 IRF1 1 hits
145 IRF3 1 hits
146 IRF6 1 hits
147 IRF7 1 hits
148 ISG20 1 hits
149 ITGAE 1 hits
150 ITGAL 1 hits
151 ITGAM 1 hits
152 ITGAX 1 hits
153 ITGB2 1 hits
154 IV 1 hits
155 JAG1 1 hits
156 JPH4 1 hits
157 JUN 1 hits
158 KLRK1 1 hits
159 KRAS 1 hits
160 LAMC2 1 hits
161 LAMP3 1 hits
162 LCK 1 hits
163 LMNA 1 hits
164 LRP1 1 hits
165 LY75 1 hits
166 MAPK1 1 hits
167 MAPK8 1 hits
168 MIPEP 1 hits
169 MLANA 1 hits
170 MRC1 1 hits
171 MS4A1 1 hits
172 MUC1 1 hits
173 MUT 1 hits
174 MYD88 1 hits
175 MYOZ3 1 hits
176 NFATC2 1 hits
177 NFKB1 1 hits
178 NFKBIA 1 hits
179 NLRP3 1 hits
180 NOD2 1 hits
181 P2RX7 1 hits
182 PAX5 1 hits
183 PDC 1 hits
184 PDCD1LG2 1 hits
185 PLP1 1 hits
186 PRDM1 1 hits
187 PRKCA 1 hits
188 PTPRC 1 hits
189 RAPH1 1 hits
190 RBL2 1 hits
191 RELB 1 hits
192 RFXANK 1 hits
193 RPS27A 1 hits
194 RRM1 1 hits
195 S100A1 1 hits
196 S11 1 hits
197 SCARA3 1 hits
198 SCYL1 1 hits
199 SEC62 1 hits
200 SELL 1 hits
201 SILV 1 hits
202 SPN 1 hits
203 SRFBP1 1 hits
204 STAT3 1 hits
205 STX1A 1 hits
206 STX1B 1 hits
207 TAOK2 1 hits
208 TAP1 1 hits
209 TBX21 1 hits
210 TGFA 1 hits
211 TGFB1 1 hits
212 TH1L 1 hits
213 TICAM1 1 hits
214 TLR1 1 hits
215 TLR2 1 hits
216 TLR3 1 hits
217 TLR4 1 hits
218 TLR7 1 hits
219 TLR9 1 hits
220 TNF 1 hits
221 TNFAIP3 1 hits
222 TNFRSF11A 1 hits
223 TNFRSF13B 1 hits
224 TNFRSF18 1 hits
225 TNFRSF1A 1 hits
226 TNFRSF4 1 hits
227 TNFRSF9 1 hits
228 TNFSF10 1 hits
229 TNFSF11 1 hits
230 TNFSF13 1 hits
231 TNFSF13B 1 hits
232 TNFSF14 1 hits
233 TNFSF18 1 hits
234 TNFSF4 1 hits
235 TOLLIP 1 hits
236 TP53 1 hits
237 TRA 1 hits
238 TRADD 1 hits
239 TRAF3 1 hits
240 TRAF6 1 hits
241 TXN 1 hits
242 TYR 1 hits
243 UBASH3B 1 hits
244 VHLL 1 hits
245 VTCN1 1 hits
246 VWS 1 hits
247 XBP1 1 hits

Related Sentences

# PMID Sentence
1 7541819 Roles of CD40 ligand and B7-2 in established germinal centers.
2 7541819 We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during the early (days -1 to 3) or late (days 6-10) phases of primary responses to thymus-dependent (Td) and -independent (Ti) Ags.
3 7541819 Our findings suggest that the costimulatory roles of CD40:CD40L and B7-2:CD28/CTLA-4 differ in the GC; administration of anti-CD40L abrogates an established GC reaction, whereas Ab to B7-2 suppresses Ig hypermutation and entry into the B cell memory compartment.
4 7541819 Once B cells have entered the differentiation pathway to Ab production, neither CD40L nor B7-2 is necessary for their continued differentiation and persistence.
5 7541819 Roles of CD40 ligand and B7-2 in established germinal centers.
6 7541819 We have compared the roles of CD40L and B7-2 in the initiation and maturation of humoral immunity by administering anti-CD40 ligand (L) or anti-B7-2 Ab during the early (days -1 to 3) or late (days 6-10) phases of primary responses to thymus-dependent (Td) and -independent (Ti) Ags.
7 7541819 Our findings suggest that the costimulatory roles of CD40:CD40L and B7-2:CD28/CTLA-4 differ in the GC; administration of anti-CD40L abrogates an established GC reaction, whereas Ab to B7-2 suppresses Ig hypermutation and entry into the B cell memory compartment.
8 7541819 Once B cells have entered the differentiation pathway to Ab production, neither CD40L nor B7-2 is necessary for their continued differentiation and persistence.
9 8149665 CD40 ligand and IL-2) for B cell survival and progression to immunoglobulin secretion.
10 8765041 Thus, dextran-conjugated anti-IgA antibody (anti-IgA-dextran), anti-kappa-dextran, or various immobilized anti-IgA antibodies (Ab) induced only low-level IgA B cell proliferation and no IgA secretion in the presence of various lymphokines; in marked contrast, sIgA+ B cells responded to cognate and noncognate T cell stimulation as well as to stimulation by CD40 ligand-bearing fibroblasts by secreting large amounts of IgA (up to 240 000 ng/ml per 10(5) cells).
11 8839846 Here, we show that the sequential use of early-acting hematopoietic growth factors, stem cell factor, interleukin (IL)-3, and IL-6, followed on day 8 by differentiation in the two-factor combination IL-4 plus granulocytemacrophage colony-stimulating factor (GM-CSF) (CC4GM) is more efficient and allows the cells to be arrested in the LC stage for more than 1 week while continuous maturation occurs in CC7-7.
12 8839846 LC were CD1a+2 DR+2, CD23+, CD36+, CD80-, CD86-, and CD25-, while DC were CD1a+/- DR+3, CD23-, CD36-, CD80+, CD86+2, and CD25+, CD40 and CD32 were moderately expressed and nearly unchanged on maturation, in contrast to monocyte-derived DC.
13 8892615 We show here that highly purified CD14(bright) peripheral blood monocytes supplemented with granulocyte-monocyte (GM)-CSF plus IL-4 develop with high efficacy (>95% of input cells) into DC.
14 8892615 They neo-expressed CD1a, CD1b, CD1c, CD80, and CD5; they massively up-regulated CD40 (109-fold) and HLA-DQ and DP (125- and 87-fold); and significantly (>5-fold) up-regulated HLA-DR, CD4, CD11b, CD11c, CD43, CD45, CD45R0, CD54, CD58, and CD59.
15 8892615 CD14, CD15s, CD64, and CDw65 molecules were down-regulated to background levels, and no major changes were observed for HLA class I, CD11a, CD32, CD33, CD48, CD50, CD86, CDw92, CD93, or CD97.
16 8892615 Monocytes cultured in parallel with GM-CSF plus TNF-alpha were more heterogeneous in expression densities but otherwise similar in their surface molecule repertoire.
17 8892615 Only GM-CSF plus IL-4-cultured cells were found to be potent stimulators in allogeneic and autologous MLR and they presented tetanus toxoid 100- to 1000-fold more efficiently than other cell populations tested.
18 9058807 However, costimulation of anti-Ig-dextran-activated neonatal B cells with either CD40-ligand, a recombinant bacterial lipoprotein, or LPS restores the IgM secretory response of neonatal B cells to adult levels.
19 9205055 Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154.
20 9205055 Interactions between CD40 and its ligand, CD154 (CD40L, gp39), have been shown to play a central role in the regulation of humoral immunity.
21 9205055 The contribution of this ligand-receptor pair to the development of protective immunity against syngeneic tumors was evaluated by blocking the in vivo function of CD154 or by studying tumor resistance in mice genetically deficient in CD40 expression (CD40-/-).
22 9205055 In the former case, anti-CD154 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Corynebacterium parvum adjuvant, and irradiated B16 melanoma cells transduced with the gene for granulocyte macrophage colony-stimulating factor.
23 9205055 Confirmation of the role of CD40/CD154 interactions in tumor immunity was provided by the overt tumor susceptibility in CD40-deficient mice as compared to that in CD40+/+ mice.
24 9205055 These findings suggest a critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines and may have important implications for future approaches to cell-based cancer therapies.
25 9205055 Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154.
26 9205055 Interactions between CD40 and its ligand, CD154 (CD40L, gp39), have been shown to play a central role in the regulation of humoral immunity.
27 9205055 The contribution of this ligand-receptor pair to the development of protective immunity against syngeneic tumors was evaluated by blocking the in vivo function of CD154 or by studying tumor resistance in mice genetically deficient in CD40 expression (CD40-/-).
28 9205055 In the former case, anti-CD154 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Corynebacterium parvum adjuvant, and irradiated B16 melanoma cells transduced with the gene for granulocyte macrophage colony-stimulating factor.
29 9205055 Confirmation of the role of CD40/CD154 interactions in tumor immunity was provided by the overt tumor susceptibility in CD40-deficient mice as compared to that in CD40+/+ mice.
30 9205055 These findings suggest a critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines and may have important implications for future approaches to cell-based cancer therapies.
31 9205055 Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154.
32 9205055 Interactions between CD40 and its ligand, CD154 (CD40L, gp39), have been shown to play a central role in the regulation of humoral immunity.
33 9205055 The contribution of this ligand-receptor pair to the development of protective immunity against syngeneic tumors was evaluated by blocking the in vivo function of CD154 or by studying tumor resistance in mice genetically deficient in CD40 expression (CD40-/-).
34 9205055 In the former case, anti-CD154 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Corynebacterium parvum adjuvant, and irradiated B16 melanoma cells transduced with the gene for granulocyte macrophage colony-stimulating factor.
35 9205055 Confirmation of the role of CD40/CD154 interactions in tumor immunity was provided by the overt tumor susceptibility in CD40-deficient mice as compared to that in CD40+/+ mice.
36 9205055 These findings suggest a critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines and may have important implications for future approaches to cell-based cancer therapies.
37 9205055 Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154.
38 9205055 Interactions between CD40 and its ligand, CD154 (CD40L, gp39), have been shown to play a central role in the regulation of humoral immunity.
39 9205055 The contribution of this ligand-receptor pair to the development of protective immunity against syngeneic tumors was evaluated by blocking the in vivo function of CD154 or by studying tumor resistance in mice genetically deficient in CD40 expression (CD40-/-).
40 9205055 In the former case, anti-CD154 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Corynebacterium parvum adjuvant, and irradiated B16 melanoma cells transduced with the gene for granulocyte macrophage colony-stimulating factor.
41 9205055 Confirmation of the role of CD40/CD154 interactions in tumor immunity was provided by the overt tumor susceptibility in CD40-deficient mice as compared to that in CD40+/+ mice.
42 9205055 These findings suggest a critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines and may have important implications for future approaches to cell-based cancer therapies.
43 9205055 Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154.
44 9205055 Interactions between CD40 and its ligand, CD154 (CD40L, gp39), have been shown to play a central role in the regulation of humoral immunity.
45 9205055 The contribution of this ligand-receptor pair to the development of protective immunity against syngeneic tumors was evaluated by blocking the in vivo function of CD154 or by studying tumor resistance in mice genetically deficient in CD40 expression (CD40-/-).
46 9205055 In the former case, anti-CD154 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Corynebacterium parvum adjuvant, and irradiated B16 melanoma cells transduced with the gene for granulocyte macrophage colony-stimulating factor.
47 9205055 Confirmation of the role of CD40/CD154 interactions in tumor immunity was provided by the overt tumor susceptibility in CD40-deficient mice as compared to that in CD40+/+ mice.
48 9205055 These findings suggest a critical role for CD40/CD154 interactions in the induction of cellular immunity by tumor vaccines and may have important implications for future approaches to cell-based cancer therapies.
49 9287173 Basic immunological research has benefited from the use of recombinant viruses to further understand the role of molecules such as CD40 ligand, nitric oxide and interleukin-4.
50 9415316 We showed that anti-CD40 mAb or CD40 ligand acts in synergy with rhIL-4 to enable the transduction of approximately 50-75% of B-CLL cells (B-CLL, n = 6).
51 9427612 T-cell help is mainly mediated through ligation of the B-cell surface antigen, CD40, by its cognate T-cell ligand, CD154.
52 9479584 This result suggests that the tumor necrosis factor receptor (TNFR) p55 plays a critical, and previously unrecognized, role in downregulating pathogen-induced inflammatory responses.
53 9489760 Antibodies to the ligand for CD40 (CD154) have been shown to exert profound effects on the development of cell-mediated immune responses in mice.
54 9550372 Immunostimulatory effects of a plasmid expressing CD40 ligand (CD154) on gene immunization.
55 9550372 Interaction of CD40 with its ligand (CD154) can induce CD40-bearing APCs to express immune stimulatory accessory molecules that facilitate immune recognition.
56 9550372 Immunostimulatory effects of a plasmid expressing CD40 ligand (CD154) on gene immunization.
57 9550372 Interaction of CD40 with its ligand (CD154) can induce CD40-bearing APCs to express immune stimulatory accessory molecules that facilitate immune recognition.
58 9622100 Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells.
59 9622100 CD70 (CD27 ligand (CD27L)), CD153 (CD30L), and CD154 (CD40L) are members of the tumor necrosis factor family of costimulatory molecules and expressed on the surface of T cells that are important for both T- and B-cell help.
60 9622100 We examined the capacity for expression of these tumor necrosis factor family members on tumor cells to induce an antitumor response either in the presence or absence of interleukin 12.
61 9622100 Retroviral vectors were constructed that expressed high levels of membrane bound CD70, CD153, or CD154 following infection and selection of the murine tumor lines MCA 207 or TS/A.
62 9622100 When tested for tumor establishment, the expression of either CD70 or CD154 was able to slow tumor growth.
63 9622100 Similarly, CD70 or CD154 were able to induce antitumor immunity at a higher frequency when tested in vaccination and therapy models.
64 9622100 CD70 was able to induce antitumor immunity at a level similar to CD80 when tested either in the presence or absence of interleukin 12.
65 9622100 Moreover, coexpression of CD70 and CD80 was able to synergize the induction of a higher frequency of antitumor immunity in a vaccination model.
66 9622100 Taken together, our results suggest that CD154 and in particular CD70 are able to contribute to the induction of the immune response to tumor in murine models and thus may be of use for human clinical trials.
67 9635447 Clones representing the three glucose phosphate isomerase (GPI) isotypes, which constituted the newly isolated virulent culture, were obtained from p3 by limiting dilution; p50 and p130 consisted of one isotype.
68 9694951 Pharmacokinetics/dynamics of 5c8, a monoclonal antibody to CD154 (CD40 ligand) suppression of an immune response in monkeys.
69 9694951 The pharmacokinetics and pharmacodynamics (PK/PD) of chimeric (Ch5c8) and humanized (Hu5c8) 5c8, a monoclonal antibody that binds CD154 (CD40 ligand), thus blocking the interaction between CD40 and CD154, were investigated in cynomolgus monkeys.
70 9694951 The monoclonal antibody 5c8 blocks the CD40 and CD154 interaction, producing consistent and substantive reduction in antibody formation after administration of tetanus toxoid, which can be characterized with PK/PD modeling.
71 9694951 Pharmacokinetics/dynamics of 5c8, a monoclonal antibody to CD154 (CD40 ligand) suppression of an immune response in monkeys.
72 9694951 The pharmacokinetics and pharmacodynamics (PK/PD) of chimeric (Ch5c8) and humanized (Hu5c8) 5c8, a monoclonal antibody that binds CD154 (CD40 ligand), thus blocking the interaction between CD40 and CD154, were investigated in cynomolgus monkeys.
73 9694951 The monoclonal antibody 5c8 blocks the CD40 and CD154 interaction, producing consistent and substantive reduction in antibody formation after administration of tetanus toxoid, which can be characterized with PK/PD modeling.
74 9694951 Pharmacokinetics/dynamics of 5c8, a monoclonal antibody to CD154 (CD40 ligand) suppression of an immune response in monkeys.
75 9694951 The pharmacokinetics and pharmacodynamics (PK/PD) of chimeric (Ch5c8) and humanized (Hu5c8) 5c8, a monoclonal antibody that binds CD154 (CD40 ligand), thus blocking the interaction between CD40 and CD154, were investigated in cynomolgus monkeys.
76 9694951 The monoclonal antibody 5c8 blocks the CD40 and CD154 interaction, producing consistent and substantive reduction in antibody formation after administration of tetanus toxoid, which can be characterized with PK/PD modeling.
77 9696840 CD40 ligand-mediated interactions are involved in the generation of memory CD8(+) cytotoxic T lymphocytes (CTL) but are not required for the maintenance of CTL memory following virus infection.
78 9696840 In this study, we investigated the involvement of CD40 ligand (CD40L)-mediated interactions in these processes by analyzing the memory CTL response of CD40L-deficient mice following infection with lymphocytic choriomeningitis virus (LCMV).
79 9696840 The maintenance of memory CD8(+) CTL precursors (CTLp) at stable frequencies over time was not impaired in CD40L-deficient mice.
80 9696840 CD40L-deficient mice produced lower levels of CD8(+) CTLp during the primary immune response to LCMV than did wild-type controls, despite the fact that the LCMV-specific effector CTL response of CD40L-deficient mice was indistinguishable from that of control animals.
81 9696840 The differentiation of naïve CD8(+) T cells into effector and memory CTL thus involves pathways that can be discriminated from each other by their requirement for CD40L-mediated interactions.
82 9696840 Expression of CD40L by CTLp themselves was not an essential step during their expansion and differentiation from naïve CD8(+) cells into memory CTLp; instead, the reduction in memory CTLp generation in CD40L-deficient mice was likely a consequence of defects in the CD4(+) T-cell response mounted by these animals.
83 9696840 These results thus suggest a previously unappreciated role for CD40L in the generation of CD8(+) memory CTLp, the probable nature of which is discussed.
84 9696840 CD40 ligand-mediated interactions are involved in the generation of memory CD8(+) cytotoxic T lymphocytes (CTL) but are not required for the maintenance of CTL memory following virus infection.
85 9696840 In this study, we investigated the involvement of CD40 ligand (CD40L)-mediated interactions in these processes by analyzing the memory CTL response of CD40L-deficient mice following infection with lymphocytic choriomeningitis virus (LCMV).
86 9696840 The maintenance of memory CD8(+) CTL precursors (CTLp) at stable frequencies over time was not impaired in CD40L-deficient mice.
87 9696840 CD40L-deficient mice produced lower levels of CD8(+) CTLp during the primary immune response to LCMV than did wild-type controls, despite the fact that the LCMV-specific effector CTL response of CD40L-deficient mice was indistinguishable from that of control animals.
88 9696840 The differentiation of naïve CD8(+) T cells into effector and memory CTL thus involves pathways that can be discriminated from each other by their requirement for CD40L-mediated interactions.
89 9696840 Expression of CD40L by CTLp themselves was not an essential step during their expansion and differentiation from naïve CD8(+) cells into memory CTLp; instead, the reduction in memory CTLp generation in CD40L-deficient mice was likely a consequence of defects in the CD4(+) T-cell response mounted by these animals.
90 9696840 These results thus suggest a previously unappreciated role for CD40L in the generation of CD8(+) memory CTLp, the probable nature of which is discussed.
91 9720647 Here we describe that aging is associated with the emergence of an unusual CD4 T cell subset characterized by the loss of CD28 expression.
92 9720647 Despite the deficiency of CD28, these unusual T cells remain functionally active and produce high concentrations of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2).
93 9720647 The loss of CD28 expression is correlated with a lack of CD40 ligand expression rendering these CD4 T cells incapable of promoting B cell differentiation and immunoglobulin secretion.
94 9720647 We propose that the emergence of CD28-deficient CD4 T cells in the elderly can partially explain age-specific aberrations in immune responsiveness.
95 9725199 A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously.
96 9725199 Herein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination.
97 9725199 These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.
98 9725199 A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously.
99 9725199 Herein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination.
100 9725199 These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.
101 9725199 A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously.
102 9725199 Herein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination.
103 9725199 These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.
104 9737667 The present study shows that Langerhans cells of the buccal mucosa and the skin share a similar phenotype, including in situ expression of MHC class II, the mannose receptor DEC-205 and CD11c, and absence of the costimulatory molecules B7.1, B7.2 and CD40 as well as Fas.
105 9737667 Buccal sensitization with DNFB elicited a specific contact sensitivity (CS) in response to skin challenge, mediated by class I-restricted CD8+ effector T cells and down-regulated by class II-restricted CD4+ T cells, demonstrated by the lack of priming of class I-deficient mice and the enhanced response of class II-deficient mice, respectively.
106 9737667 Thus, the buccal epithelium is an inductive site, equivalent to the epidermis, for the generation of CS independent of CD4 help, and of cytotoxic T lymphocyte (CTL) responses mediated by class I-restricted CD8+ T cells.
107 9794383 CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge.
108 9794383 CD40/CD40 ligand interactions have a central role in the induction of both humoral and cellular immunity.
109 9794383 In this study, we examined whether a plasmid expressing CD40 ligand/trimer (CD40LT) could enhance immune responses in vivo.
110 9794383 CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge.
111 9794383 CD40/CD40 ligand interactions have a central role in the induction of both humoral and cellular immunity.
112 9794383 In this study, we examined whether a plasmid expressing CD40 ligand/trimer (CD40LT) could enhance immune responses in vivo.
113 9794383 CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge.
114 9794383 CD40/CD40 ligand interactions have a central role in the induction of both humoral and cellular immunity.
115 9794383 In this study, we examined whether a plasmid expressing CD40 ligand/trimer (CD40LT) could enhance immune responses in vivo.
116 9796737 Such Ts cells express the CD8+CD28- phenotype and show the following characteristics: (a) antigen specificity and restriction by self MHC Class I molecules; (b) limited TCR V beta gene usage; (c) ability to inhibit antigen-specific, MHC Class II restricted, Th proliferative responses; and (d) capacity to downregulate and/or inhibit the upregulation by Th of CD40, CD80, and CD86 molecules on APCs.
117 9886383 BmDC cultured under various conditions (granulocyte-macrophage CSF (GM-CSF) or GM-CSF plus IL-4 alone or in combination with Flt3 ligand, TNF-alpha, LPS, or CD40 ligand (CD40L)) were analyzed morphologically, phenotypically, and functionally and were tested for their ability to promote prophylactic and/or therapeutic antitumor immunity.
118 9886383 Whereas cells cultured in GM-CSF alone were functionally immature, cells incubated with CD40L or LPS were mature BmDC, as evident by morphology, capacity to internalize Ag, migration into regional lymph nodes, IL-12 secretion, and alloantigen or peptide Ag presentation in vitro.
119 9973457 Mucosally induced systemic T cell unresponsiveness to ovalbumin requires CD40 ligand-CD40 interactions.
120 9973457 CD40 ligand (CD40L) gene-disrupted (CD40L-/-) mice were employed to examine the role of costimulatory signals via CD40L-CD40 interactions in mucosally induced tolerance.
121 9973457 Further, cytokine analysis of splenic CD4+ T cells showed that both Th1-type (e.g., IFN-gamma and IL-2) and Th2-type (e.g., IL-4, IL-5, IL-6, and IL-10) responses were maintained in CD40L-/- mice orally immunized with OVA, whereas these cytokine responses in CD40L+/+ mice were significantly reduced.
122 9973457 In addition, splenic CD4+ T cells from CD40L-/- mice orally immunized with OVA provided B cell help in Ag-specific Ab-forming cells when the cells were cultured with naive B cells in the presence of Ag and CD40L-transfected cell lines.
123 9973457 In contrast, an identical culture condition containing splenic CD4+ T cells from orally tolerized CD40L+/+ mice did not exhibit helper activity.
124 9973457 Taken together, these findings indicate that CD40L and CD40 interactions are essential for the induction of systemic T cell unresponsiveness to orally administered Ag.
125 9973457 Mucosally induced systemic T cell unresponsiveness to ovalbumin requires CD40 ligand-CD40 interactions.
126 9973457 CD40 ligand (CD40L) gene-disrupted (CD40L-/-) mice were employed to examine the role of costimulatory signals via CD40L-CD40 interactions in mucosally induced tolerance.
127 9973457 Further, cytokine analysis of splenic CD4+ T cells showed that both Th1-type (e.g., IFN-gamma and IL-2) and Th2-type (e.g., IL-4, IL-5, IL-6, and IL-10) responses were maintained in CD40L-/- mice orally immunized with OVA, whereas these cytokine responses in CD40L+/+ mice were significantly reduced.
128 9973457 In addition, splenic CD4+ T cells from CD40L-/- mice orally immunized with OVA provided B cell help in Ag-specific Ab-forming cells when the cells were cultured with naive B cells in the presence of Ag and CD40L-transfected cell lines.
129 9973457 In contrast, an identical culture condition containing splenic CD4+ T cells from orally tolerized CD40L+/+ mice did not exhibit helper activity.
130 9973457 Taken together, these findings indicate that CD40L and CD40 interactions are essential for the induction of systemic T cell unresponsiveness to orally administered Ag.
131 9973457 Mucosally induced systemic T cell unresponsiveness to ovalbumin requires CD40 ligand-CD40 interactions.
132 9973457 CD40 ligand (CD40L) gene-disrupted (CD40L-/-) mice were employed to examine the role of costimulatory signals via CD40L-CD40 interactions in mucosally induced tolerance.
133 9973457 Further, cytokine analysis of splenic CD4+ T cells showed that both Th1-type (e.g., IFN-gamma and IL-2) and Th2-type (e.g., IL-4, IL-5, IL-6, and IL-10) responses were maintained in CD40L-/- mice orally immunized with OVA, whereas these cytokine responses in CD40L+/+ mice were significantly reduced.
134 9973457 In addition, splenic CD4+ T cells from CD40L-/- mice orally immunized with OVA provided B cell help in Ag-specific Ab-forming cells when the cells were cultured with naive B cells in the presence of Ag and CD40L-transfected cell lines.
135 9973457 In contrast, an identical culture condition containing splenic CD4+ T cells from orally tolerized CD40L+/+ mice did not exhibit helper activity.
136 9973457 Taken together, these findings indicate that CD40L and CD40 interactions are essential for the induction of systemic T cell unresponsiveness to orally administered Ag.
137 10395323 Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40.
138 10395323 We therefore assessed the fate of tumor-specific CD4+ T cells in tumor-bearing recipients after in vivo activation of antigen-presenting cells with antibodies against CD40.
139 10395323 Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40.
140 10395323 We therefore assessed the fate of tumor-specific CD4+ T cells in tumor-bearing recipients after in vivo activation of antigen-presenting cells with antibodies against CD40.
141 10395322 The outcome of antigen recognition by naive CD8+ cytotoxic T lymphocytes (CTLs) in the periphery is orchestrated by CD4+ T-helper cells, and can either lead to priming or tolerization.
142 10395322 These findings indicate that the CD40-CD40 ligand pair can act as a 'switch', determining whether naive peripheral CTLs are primed or tolerized, and support the clinical use of CD40-stimulating agents as components of anti-cancer vaccines.
143 10413189 Serum has been analyzed for IgE, specific titers to Rubella vaccine, sCD25 (the soluble form of the IL2 receptor), sCD27 (the soluble form of the lymphocyte specific member of the tumor necrosis factor receptor family), and IL4 (the cytokine interleukin 4).
144 10415005 Cutting edge: CD40 ligand is a limiting factor in the humoral response to T cell-dependent antigens.
145 10415005 CD40 ligand (CD40L) plays a crucial role in T cell-dependent B cell responses, but whether its abundance is a limiting factor in their development is unclear.
146 10415005 This question was addressed in transgenic mice expressing the murine CD40L gene under the control of the IL-2-promoter (CD40Ltg+).
147 10415005 Cutting edge: CD40 ligand is a limiting factor in the humoral response to T cell-dependent antigens.
148 10415005 CD40 ligand (CD40L) plays a crucial role in T cell-dependent B cell responses, but whether its abundance is a limiting factor in their development is unclear.
149 10415005 This question was addressed in transgenic mice expressing the murine CD40L gene under the control of the IL-2-promoter (CD40Ltg+).
150 10429676 Dendritic cells infiltrating tumors cotransduced with granulocyte/macrophage colony-stimulating factor (GM-CSF) and CD40 ligand genes take up and present endogenous tumor-associated antigens, and prime naive mice for a cytotoxic T lymphocyte response.
151 10429676 We transduced BALB/c-derived C-26 colon carcinoma cells with granulocyte/macrophage colony-stimulating factor (GM-CSF) and CD40 ligand (CD40L) genes to favor interaction of these cells with host dendritic cells (DCs) and, therefore, cross-priming.
152 10429676 DCs isolated from C-26/GM/CD40L tumors grown in (BALB/c x C57BL/6)F1 mice (H-2d x b) stimulated interferon gamma production by both anti-AH-1 and KSP CTLs, whereas tumor-infiltrating DCs (TIDCs) of BALB/c mice stimulated only anti-AH-1 CTLs.
153 10429676 These data indicate that DCs infiltrating tumors that produce GM-CSF and CD40L can capture cellular antigens, likely through uptake of apoptotic bodies, and mature in situ to a stage suitable for antigen presentation.
154 10429676 Dendritic cells infiltrating tumors cotransduced with granulocyte/macrophage colony-stimulating factor (GM-CSF) and CD40 ligand genes take up and present endogenous tumor-associated antigens, and prime naive mice for a cytotoxic T lymphocyte response.
155 10429676 We transduced BALB/c-derived C-26 colon carcinoma cells with granulocyte/macrophage colony-stimulating factor (GM-CSF) and CD40 ligand (CD40L) genes to favor interaction of these cells with host dendritic cells (DCs) and, therefore, cross-priming.
156 10429676 DCs isolated from C-26/GM/CD40L tumors grown in (BALB/c x C57BL/6)F1 mice (H-2d x b) stimulated interferon gamma production by both anti-AH-1 and KSP CTLs, whereas tumor-infiltrating DCs (TIDCs) of BALB/c mice stimulated only anti-AH-1 CTLs.
157 10429676 These data indicate that DCs infiltrating tumors that produce GM-CSF and CD40L can capture cellular antigens, likely through uptake of apoptotic bodies, and mature in situ to a stage suitable for antigen presentation.
158 10449160 The induction of secretion call be mediated by engagement of CD40 on dendritic cells, as indicated by the increased amount of interleukin-18 in dendritic cell supernatants after CD40 triggering by anti-CD40 antibodies.
159 10449160 However, CD40 engagement, unlike from antigen-specific T cells, does not result in reduced intracellular interleukin-18 content, suggesting that this decrease may be mediated by structure(s) involved in antigen recognition.
160 10449160 The induction of secretion call be mediated by engagement of CD40 on dendritic cells, as indicated by the increased amount of interleukin-18 in dendritic cell supernatants after CD40 triggering by anti-CD40 antibodies.
161 10449160 However, CD40 engagement, unlike from antigen-specific T cells, does not result in reduced intracellular interleukin-18 content, suggesting that this decrease may be mediated by structure(s) involved in antigen recognition.
162 10477566 DCs incubated with recombinant S. gordonii were much more efficient than DCs pulsed with soluble C-fragment of tetanus toxin at stimulating specific CD4+ T cells as determined by cell proliferation and IFN-gamma release.
163 10477566 In particular, S. gordonii dose-dependently up-regulated expression of membrane molecules (MHC I and II, CD80, CD86, CD54, CD40, CD83) and reduced both phagocytic and endocytic activities.
164 10477566 Furthermore, bacteria promoted in a dose-dependent manner DC release of cytokines (IL-6, TNF-alpha, IL-1beta, IL-12, TGF-beta, and IL-10) and of the chemokines IL-8, RANTES, IFN-gamma-inducible protein-10, and monokine induced by IFN-gamma.
165 10486153 They expressed a set of DC-associated markers, such as MHC class II, CD1a, CD4, CD11a, CD40, CD58, CD80, CD83, CD86, and CXCR4.
166 10498601 Rapid induction of CD40 on a subset of granulocyte colony-stimulating factor-mobilized CD34(+) blood cells identifies myeloid committed progenitors and permits selection of nonimmunogenic CD40(-) progenitor cells.
167 10498601 CD40 antigen is a costimulatory molecule highly expressed on dendritic cells (DC) and activated B cells, which induces T-cell proliferation through the binding with CD40L receptor.
168 10498601 CD40, CD80, and CD86 antigens were constitutively expressed on 3.2% +/- 4.5%, 0%, and 1.8% +/- 1.2% CD34(+) blood cells, respectively.
169 10498601 However, after 24 hours in liquid culture with medium alone, or with tumor-necrosis-factor-alpha (TNF-alpha), or with allogeneic mononuclear cells 10.8% +/- 3.8%, 75.3% +/- 15.0% and 53. 7% +/- 17.0% CD34(+) blood cells, respectively, became CD40(+).
170 10498601 After incubation for 24 hours with TNF-alpha CD34(+)CD40(+) blood cells expressed only myeloid markers and contained less than 5% CD86(+) and CD80(+) cells.
171 10498601 Also, a 24-hour priming with TNF-alpha or ligation of CD40 significantly increased the CD34(+) blood cells alloantigen presenting function.
172 10498601 Finally, purified CD34(+)CD40(+) blood cells stimulated an alloreactive T-cell response in MLC, were enriched in granulocytic, monocytic, and dendritic precursors, and generated high numbers of DC in 11-14 d liquid cultures with GM-CSF, SCF, TNF-alpha and FLT-3L.
173 10498601 In conclusion, a short incubation with TNF-alpha allows the selection of CD40(+) blood progenitors, which may be a useful source of DC precursors for antitumor vaccine studies, and also a CD34(+)CD40(-) blood cell fraction that could be exploited in innovative strategies of allogeneic transplantation across HLA barriers.
174 10555997 Previously, we demonstrated that a novel low-molecular-weight synthetic immune response modifier, R-848, induces IL-12 and IFN-alpha secretion from monocytes and macrophages.
175 10555997 Characteristic of dendritic cell maturation, R-848 treatment induces cell surface expression of CD83 and increases cell surface expression of CD80, CD86, CD40, and HLA-DR.
176 10555997 Additionally, R-848 induces cytokine (IL-6, IL-12, TNF-alpha, IFN-alpha) and chemokine (IL-8, MIP-1alpha, MCP-1) secretion from dendritic cells.
177 10559341 We now show that infection by rAd enhances the immunostimulatory capacity of immature human monocyte-derived DC through the upregulation of the costimulatory molecules CD80, CD86, and CD40 and the major histocompatibility complex class I and II molecules.
178 10559341 Although rAd infection fails to induce the secretion of interleukin-12 (IL-12) and only marginally induces the expression of the DC maturation marker CD83, it acts in synergy with CD40 triggering in rendering DC fully mature. rAd-infected DC triggered through CD40 produce more IL-12 and are more efficient in eliciting T-helper type 1 responses than DC activated by CD40 triggering only. rAd lacking one or more of the early regions, E1, E2A, E3, and E4, which play an important role in virus-host cell interactions are equally capable of DC activation.
179 10559341 We now show that infection by rAd enhances the immunostimulatory capacity of immature human monocyte-derived DC through the upregulation of the costimulatory molecules CD80, CD86, and CD40 and the major histocompatibility complex class I and II molecules.
180 10559341 Although rAd infection fails to induce the secretion of interleukin-12 (IL-12) and only marginally induces the expression of the DC maturation marker CD83, it acts in synergy with CD40 triggering in rendering DC fully mature. rAd-infected DC triggered through CD40 produce more IL-12 and are more efficient in eliciting T-helper type 1 responses than DC activated by CD40 triggering only. rAd lacking one or more of the early regions, E1, E2A, E3, and E4, which play an important role in virus-host cell interactions are equally capable of DC activation.
181 10583605 Immunomodulatory effect of a plasmid expressing CD40 ligand on DNA vaccination against human immunodeficiency virus type-1.
182 10583605 CD40 ligand is a costimulatory molecule which acts a potent immunomodulator.
183 10583605 We found the mice inoculated with human CD40 ligand expression plasmid (pMEhCD40L) combined with human immunodeficiency virus type-1 (HIV-1) DNA vaccine exhibited both humoral and cellular antigen-specific immunological enhancement.
184 10583605 The expression of hCD40L induced predominantly antigen-specific immunoglobulin G (IgG) antibody response while it failed to induce mucosal IgA response.
185 10583605 Immunomodulatory effect of a plasmid expressing CD40 ligand on DNA vaccination against human immunodeficiency virus type-1.
186 10583605 CD40 ligand is a costimulatory molecule which acts a potent immunomodulator.
187 10583605 We found the mice inoculated with human CD40 ligand expression plasmid (pMEhCD40L) combined with human immunodeficiency virus type-1 (HIV-1) DNA vaccine exhibited both humoral and cellular antigen-specific immunological enhancement.
188 10583605 The expression of hCD40L induced predominantly antigen-specific immunoglobulin G (IgG) antibody response while it failed to induce mucosal IgA response.
189 10583605 Immunomodulatory effect of a plasmid expressing CD40 ligand on DNA vaccination against human immunodeficiency virus type-1.
190 10583605 CD40 ligand is a costimulatory molecule which acts a potent immunomodulator.
191 10583605 We found the mice inoculated with human CD40 ligand expression plasmid (pMEhCD40L) combined with human immunodeficiency virus type-1 (HIV-1) DNA vaccine exhibited both humoral and cellular antigen-specific immunological enhancement.
192 10583605 The expression of hCD40L induced predominantly antigen-specific immunoglobulin G (IgG) antibody response while it failed to induce mucosal IgA response.
193 10601552 Human tumor antigens when presented appropriately (with costimulatory molecules and with IL-2, IL-12) break the host's natural tolerance toward its tumor and induce rejection strength immune reactions even in patients with metastatic disease.
194 10601552 For successful active specific immunization against human cancers the understanding of the immunoevasive maneuvers of the tumor cell (through FasL --> Fas; TRAIL; CD40L --> CD40; TGFbeta etc. systems) is essential.
195 10607486 After a 6-h incubation, phenotypic analysis of control-, imiquimod-, or R-848-treated LC indicated that such antigen-presenting cells were in an "intermediate" state of maturation (CD1a(+), HLA-DR, DP, DQ(bright+), CD40(low+), CD86(high+), and CD80(low+)).
196 10607486 RNase protection assays demonstrated that either imiquimod or R-848 treatments increased steady-state transcripts encoding for IL-12 p40, IL-1beta, TNF-alpha, and IL-1 receptor antagonist by LC.
197 10623847 However, a role for IL-10, B7.1, and CD40 expression in Th2 response inhibition was suggested.
198 10623847 The role of IL-10 was demonstrated in mice exhibiting combined deficiencies in IL-12 and IL-10.
199 10623847 Here, a marked increase in egg-specific IL-4/IL-5-producing cells confirmed a role for both cytokines in Th2 response inhibition.
200 10623847 However, in marked contrast to IL-12-deficient animals, a significant increase in IFN-gamma-producing cells likely explains the reduced Th2 response in IL-10/IL-12-deficient mice.
201 10623847 Thus, a novel IL-12-independent type 1-inducing pathway was revealed in the combined absence of IL-12 and IL-10.
202 10623847 Together, these data demonstrate 1) that the Th1-promoting activity of CpG DNA is controlled by IL-12 and IL-10, and 2) that Th2 response inhibition by CpG ODN involves IL-12-independent changes in IL-10 and costimulatory molecule expression.
203 10679086 We demonstrate that immature and CD40 ligand-matured monocyte-derived DC have characteristic phenotypic and functional differences in vitro.
204 10679086 In particular, immature DC express CC chemokine receptor 5 (CCR5) and migrate in response to macrophage inflammatory protein-1alpha (MIP-1alpha), whereas mature DC switch expression to CCR7 and respond exclusively to MIP-3beta and 6Ckine.
205 10687141 Although a comparable percentage of DCs expressing CD86+ (B7-2), CD40+, and HLA-DR+ were detected in both cultures, higher expression levels were detected in DCs derived from bulk culture (CD86 = MRLFI 3665.1 versus 2662.1 on day 6; CD40 = MRLFI 1786 versus 681.2 on day 6; HLA-DR = MRLFI 6018.2 versus 3444.9 on day 2).
206 10687141 Cytokines involved in DC maturation were determined by polymerase chain reaction demonstrating interleukin-6 (IL-6), IL-12, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha mRNA expression by bulk culture cells during the entire 9-day culture period.
207 10687141 Concurrently, CD3+ CD56-, CD3+ CD25+, and CD3+ TCR+ cell populations increased and cytotoxicity against autologous renal cell carcinoma tumor target was induced.
208 10811863 In contrast, vaccination with granulocyte/macrophage colony-stimulating factor (GM-CSF)-transduced tumor cells, previously shown to induce potent antitumor immunity in standard tumor challenge assays, led to a decreased therapeutic effect in the metastasis model and no effect in the subcutaneous tumor model.
209 10811863 Further engineering of DCs to express either GM-CSF, tumor necrosis factor alpha, or CD40 ligand via retroviral-mediated gene transfer, led to a significantly increased therapeutic effect in the subcutaneous tumor model.
210 10811863 The immunological mechanism, as shown for GM-CSF-transduced DCs, involves MAGE-1-specific CD4(+) and CD8(+) T cells.
211 10820273 CD40 ligand (CD154) enhances the Th1 and antibody responses to respiratory syncytial virus in the BALB/c mouse.
212 10820273 CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed mainly by activated T cells.
213 10820273 CD40L expression promotes Th1 cytokine responses to protein Ags and is responsible for Ig isotype switching in B cells.
214 10820273 These studies show that coincident expression of CD40L enhances the Th1 (IL-2 and IFN-gamma) cytokine responses, increases the expression of TNF-alpha and NO, accelerates virus clearance, and increases the anti-F and anti-G Ab responses.
215 10820273 CD40 ligand (CD154) enhances the Th1 and antibody responses to respiratory syncytial virus in the BALB/c mouse.
216 10820273 CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed mainly by activated T cells.
217 10820273 CD40L expression promotes Th1 cytokine responses to protein Ags and is responsible for Ig isotype switching in B cells.
218 10820273 These studies show that coincident expression of CD40L enhances the Th1 (IL-2 and IFN-gamma) cytokine responses, increases the expression of TNF-alpha and NO, accelerates virus clearance, and increases the anti-F and anti-G Ab responses.
219 10866318 Genetically modified dendritic cells prime autoreactive T cells through a pathway independent of CD40L and interleukin 12: implications for cancer vaccines.
220 10866318 Genetic immunization through ex vivo transduction of dendritic cells has been suggested as an effective approach to enhance antitumor immunity by activating both CD4+ and CD8+ T cells.
221 10866318 Immunizing mice with dendritic cells transduced with an adenovirus expressing the human melanoma antigen glycoprotein 100 (DCAdhgp100) as a cancer vaccine, we demonstrated complete protective immunity and a potent CTL response against melanomas expressing murine glycoprotein 100 in a CD4+ cell-dependent manner.
222 10866318 Surprisingly, however, effective tumor rejection was not the result of cooperation between CD4+ and CD8+ T cells.
223 10866318 Protective immunity was completely lost when CD4+ cells were depleted immediately before tumor challenge, whereas it was unaffected by removal of CD8+ cells, establishing a principal role for CD4+ cells in the effector phase of tumor rejection.
224 10866318 Neither protective immunity nor CTL generation in this model required interleukin 12, in spite of high levels of IFN-gamma secretion by tumor-reactive T cells.
225 10866318 Most notably, the DCAdhgp100 vaccine could elicit protective antitumor CD4+ cells in the absence of CD40 ligand, although it does not bypass the need for CD40-mediated signals to generate melanoma-reactive CTLs.
226 10866318 Thus, in contrast to the current thinking that the optimal cancer vaccine should include determinants for both CD4+ and CD8+ cells, the potency of the DCAdhgp100 vaccine appears to be a result of its ability to directly prime autoreactive CD4+ cells through a process that does not require interleukin 12 and CD40 signals.
227 10866318 Genetically modified dendritic cells prime autoreactive T cells through a pathway independent of CD40L and interleukin 12: implications for cancer vaccines.
228 10866318 Genetic immunization through ex vivo transduction of dendritic cells has been suggested as an effective approach to enhance antitumor immunity by activating both CD4+ and CD8+ T cells.
229 10866318 Immunizing mice with dendritic cells transduced with an adenovirus expressing the human melanoma antigen glycoprotein 100 (DCAdhgp100) as a cancer vaccine, we demonstrated complete protective immunity and a potent CTL response against melanomas expressing murine glycoprotein 100 in a CD4+ cell-dependent manner.
230 10866318 Surprisingly, however, effective tumor rejection was not the result of cooperation between CD4+ and CD8+ T cells.
231 10866318 Protective immunity was completely lost when CD4+ cells were depleted immediately before tumor challenge, whereas it was unaffected by removal of CD8+ cells, establishing a principal role for CD4+ cells in the effector phase of tumor rejection.
232 10866318 Neither protective immunity nor CTL generation in this model required interleukin 12, in spite of high levels of IFN-gamma secretion by tumor-reactive T cells.
233 10866318 Most notably, the DCAdhgp100 vaccine could elicit protective antitumor CD4+ cells in the absence of CD40 ligand, although it does not bypass the need for CD40-mediated signals to generate melanoma-reactive CTLs.
234 10866318 Thus, in contrast to the current thinking that the optimal cancer vaccine should include determinants for both CD4+ and CD8+ cells, the potency of the DCAdhgp100 vaccine appears to be a result of its ability to directly prime autoreactive CD4+ cells through a process that does not require interleukin 12 and CD40 signals.
235 10899844 Adaptive immunity against Listeria monocytogenes in the absence of type I tumor necrosis factor receptor p55.
236 10899844 Tumor necrosis factor (TNF) and the type I TNF receptor (TNFRI), p55, are critical for resistance against primary infections with the intracellular bacterial pathogen Listeria monocytogenes.
237 10915850 Monocytes (Mo) were isolated by leukapheresis from 12 donors, purified by elutriation and then cultured for 6 days in sealed bags in AIM-V serum free medium with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-13 (IL-13).
238 10915850 Cells displayed a characteristic iDC phenotype (CD1a(+), CD14(-), CD80(+), CD86(+), HLA DR(+), CD83(-)), and had potent allogeneic and antigen dependent autologous T cell-stimulatory capacity.
239 10915850 Moreover, iDC could be further differentiated into mature DC by CD40 ligation as assessed by CD83 expression and the upregulation of HLA-DR and costimulatory molecules.
240 10918477 Ad infection (MOI 200) of BMDC induced significant increases in IL 12 p40 protein in culture supernatants (6 x that of uninfected BMDC and similar to that observed with addition of LPS and CD40 crosslinking antibody).
241 10918477 Consistent with DC activation, FACs analysis showed BMDC infected with Ad vectors up-regulated the surface expression of B7-2, ICAM-1 and MHC II.
242 10918477 Additional experiments evaluated the role of virus attachment, internalization and gene expression using IL-12 p40 production as a marker of DC activation.
243 10918477 Neither heat-inactivated Ad nor peptides containing the RGD sequence (the primary component of Ad penton base which interacts with cell surface integrins) induced significant amounts of IL12 p40.
244 10918477 In contrast, psoralen/UV-inactivated Ad showed similar levels of IL12 p40 production compared with intact Ad.
245 10948138 GXM-APC (or APC) immunization caused small increases in the expression of type-2 cytokines (IL-4 and IL-5), but the increases were not always statistically significant.
246 10948138 The CFA-induced PEC had an activated phenotype characterized by increased numbers of F4/80(+) cells that expressed CD40, B7-1, and B7-2 on their membranes.
247 11015437 B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine.
248 11015437 BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis.
249 11015437 Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL.
250 11015437 In either resting or CD40L-activated B cells, the NF-kappaB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival.
251 11015437 The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response.
252 11015437 B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine.
253 11015437 BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis.
254 11015437 Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL.
255 11015437 In either resting or CD40L-activated B cells, the NF-kappaB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival.
256 11015437 The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response.
257 11029527 The growth rates of both vaccines in murine macrophages were the same, however, Onco-BCG induced stronger and longer-lasting secretion of TNF-alpha, IL-6 and nitric oxide.
258 11029527 Onco-vaccine was also more potent in inducing NF-kappaB p65/p50 DNA-binding activity whilst in ID-BCG-infected cells the activity was transient and then gradually replaced by the transcriptionally inactive homodimer p50/p50.
259 11043379 CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity.
260 11043379 The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling.
261 11043379 Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL.
262 11043379 Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body.
263 11043379 CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity.
264 11043379 The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling.
265 11043379 Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL.
266 11043379 Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body.
267 11043379 CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity.
268 11043379 The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling.
269 11043379 Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL.
270 11043379 Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body.
271 11043379 CD40 and CD40 ligand (CD40L) have been implicated as important molecules for the transformation of nonactivated antigen-presenting cells (APC) into cells that are potent inducers of cytotoxic T lymphocyte (CTL) immunity.
272 11043379 The onset of a successful immune response lies within the control of the CD4+ T helper cells which, after specific antigen recognition, can up-regulate CD40L and subsequently activate APC through CD40 signaling.
273 11043379 Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL.
274 11043379 Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body.
275 11043847 CD40 activation enhances the magnitude of cellular immune responses against p53 but not the avidity of the effectors.
276 11049018 Recent studies, for example, indicate that the stealth-like phenotype of leukemia cells can be reversed through transfer of genes such as the one encoding CD154, the ligand for CD40.
277 11049026 A number of cell surface antigens on malignant plasma cells and/or B cells in MM and/or WM patients have been proposed for use in tumor cell-targeted serotherapy, including immunoglobulin idiotype, CD19, CD20, CD38, CD54, CD138, HM1.24, and MUC1 core protein.
278 11049026 Ongoing clinical trials are examining serotherapy targeting CD20 (in MM and WM) and CD38 (in MM), with early reports of responses to the anti-CD20 monoclonal antibody (mAb) Rituximab (Genentech, South San Francisco, CA) in patients with WM and certain patients with MM.
279 11049026 The use of agents to induce MM- and WM-selective antigens for targeting in serotherapy has been proposed based on studies demonstrating the upregulation of CD20 by interferon-gamma (IFN-gamma), and of MUC1 core protein by dexamethasone (DEX) on malignant plasma cells.
280 11049026 Whole tumor vaccination strategies are also being examined and include the use of MM cells transfected and/or stimulated with cytokines, costimulatory molecules, or CD40 ligand.
281 11053627 Influenza vaccine stimulated significantly lower production of interferon-gamma (IFN-gamma) compared with live and heat inactivated viruses, whereas both vaccine and heat-inactivated influenza induced lower levels of IFN-alpha compared with live virus.
282 11053627 A significant increase in monocyte expression of CD80, CD86, CD40, and human leukocyte antigen-DR (HLA-DR) was also induced by live influenza virus.
283 11053627 Our results suggest that immunization with live influenza vaccines might induce immune responses that would not be induced by conventional inactivated vaccines, including CTL generation, antiviral IFN-gamma and IFN-alpha cytokine production, and increased antigen presentation and costimulatory capacity on antigen presenting cells (APC).
284 11069291 This phenomenon could be mimicked in part by signaling either through CD40 to the antigen-presenting cells or through OX40 to the tumor-determinant reactive T cells, with maximal effects obtained by combined anti-CD40 and anti-OX40 treatment in vivo.
285 11086107 Dendritic cells, infected with vesicular stomatitis virus-pseudotyped HIV-1, present viral antigens to CD4+ and CD8+ T cells from HIV-1-infected individuals.
286 11086107 The nonreplicating, VSV/HIV-1 efficiently infected the immature stage of DC development, in this case represented by monocytes cultured with GM-CSF and IL-4.
287 11086107 The infected populations were further matured with CD40 ligand, leading to strong stimulation of autologous T cells from HIV-1-infected individuals, but not controls.
288 11086107 Enriched CD8(+) T cells from 12/12 donors released IFN-gamma (50-300 enzyme-linked immunospots/200,000 T cells) and proliferated.
289 11086107 Presentation to CD8(+) T cells, but not to CD4(+), was primarily through an endogenous pathway, because the responses were markedly reduced if envelope-defective virus particles or reverse transcriptase inhibitors were added.
290 11086107 Therefore, nonreplicating vaccines can be targeted to immature DCs, which upon further maturation induce combined and robust CD4(+) and CD8(+) immunity.
291 11106934 Selection and characterization of MUC1-specific CD8+ T cells from MUC1 transgenic mice immunized with dendritic-carcinoma fusion cells.
292 11106934 Here we demonstrate that lymph node cells from MUC1.Tg mice immunized with the FC/MUC1 fusion cells proliferate in response to MUC1 antigen by a mechanism dependent on the function of CD4, major histocompatibility complex (MHC) class II, B7-1, B7-2, CD28, CD40 and CD40 ligand.
293 11106934 The findings demonstrate that stimulation of lymph node cells with MUC1 results in selection of MUC1-specific CD8+ T cells.
294 11106934 We show that the CD8+ T cells exhibit MUC1-specific cytotoxic T lymphocyte (CTL) activity by recognition of MUC1 peptides presented in the context of MHC class I molecules Kb and Db.
295 11106934 The MUC1-specific CD8+ T cells also exhibit antitumour activity against MUC1-positive metastases, but with no apparent reactivity against normal tissues.
296 11106934 These results indicate that immunization of MUC1.Tg mice with FC/MUC1 reverses immunological unresponsiveness to MUC1 by presentation of MUC1 peptides in the presence of costimulatory signals and generates MHC-restricted MUC1-specific CD8+ T cells.
297 11160013 Thus, flow cytometry analyses showed an increase in the expression of major histocompatibility complex (MHC) class II, CD40, CD54, CD58, CD83, and CD86 molecules on the monocytes.
298 11160013 The increase in cell surface expression of MHC class II did not occur in the presence of neutralizing IL-4 antibody or in cultures of highly purified monocytes or CD4-depleted mononuclear cells.
299 11160013 Activated Th2 cells release IL-4, which in turn can induce an increase in the expression of MHC class II molecules on monocytes.
300 11207256 However, the increased surface expression of CD40 and B7 on these dendritic cells is insufficient to overcome the need for MHC class II-restricted CD4(+) T cell help in the priming of a CTL response.
301 11207297 Infection of CD40- or MHC class II-deficient mice induced poor CD8 T cell responses in the intestinal mucosa, but only partially reduced responses in the spleen and liver.
302 11223075 An integral and necessary part of a T-cell immune response involves triggering of CD40 on antigen-presenting cells (APC) by its ligand, CD154, on responding T helper (Th) cells.
303 11223075 Furthermore, cytotoxic responses to tumours may fail because the Th-cell response is inadequate and unable to provide CD40 stimulation of APC.
304 11223075 Growing evidence shows that stimulating APC with soluble CD40L or an agonistic anti-CD40 mAb can, at least in part, replace the need for Th cells and generate APC that are capable of priming cytotoxic T lymphocytes (CTL).
305 11223075 In addition, depletion of CD8(+) cells abrogated protection whilst depletion of CD4(+) cells had no effect.
306 11223075 An integral and necessary part of a T-cell immune response involves triggering of CD40 on antigen-presenting cells (APC) by its ligand, CD154, on responding T helper (Th) cells.
307 11223075 Furthermore, cytotoxic responses to tumours may fail because the Th-cell response is inadequate and unable to provide CD40 stimulation of APC.
308 11223075 Growing evidence shows that stimulating APC with soluble CD40L or an agonistic anti-CD40 mAb can, at least in part, replace the need for Th cells and generate APC that are capable of priming cytotoxic T lymphocytes (CTL).
309 11223075 In addition, depletion of CD8(+) cells abrogated protection whilst depletion of CD4(+) cells had no effect.
310 11228391 Plasmids encoding granulocyte-macrophage colony-stimulating factor and CD154 enhance the immune response to genetic vaccines.
311 11228391 We examined whether plasmids encoding granulocyte-macrophage colony-stimulating factor (pGM-CSF) or CD40-ligand (pCD40L) could modify the immune response to antigen encoded by co-injected plasmid DNA.
312 11228391 We conclude that plasmids encoding GM-CSF and CD154 are particularly effective genetic adjuvants when used together to enhance the humoral and cellular immune response to a plasmid-encoded antigen.
313 11238201 Up-regulation of CD40 ligand and induction of a Th2 response in children immunized with pneumococcal polysaccharide vaccines.
314 11238201 We wished to determine whether pneumococcal polysaccharide antigens induce mRNA expression of CD40 ligand (CD40L) and Th1 or Th2 cytokines in unimmunized individuals in vitro and whether immunization with the 23-valent pneumococcal polysaccharide vaccine induces changes in CD40L and cytokine mRNA expression.
315 11238201 Quantification of mRNA expression of CD40L, interleukin-4 (IL-4), IL-12p40, and gamma interferon (IFN-gamma) was performed by reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA)-PCR with resting and stimulated peripheral blood mononuclear cells.
316 11238201 The results showed a significant increase in the expression of mRNAs for CD40L and IL-4, but not IL-12p40 or IFN-gamma, in stimulated cultures from unimmunized individuals.
317 11238201 CD40L and IL-4 mRNA expression was significantly higher in postimmunization than in preimmunization samples stimulated with the individual pneumococcal serotypes.
318 11238201 Up-regulation of CD40 ligand and induction of a Th2 response in children immunized with pneumococcal polysaccharide vaccines.
319 11238201 We wished to determine whether pneumococcal polysaccharide antigens induce mRNA expression of CD40 ligand (CD40L) and Th1 or Th2 cytokines in unimmunized individuals in vitro and whether immunization with the 23-valent pneumococcal polysaccharide vaccine induces changes in CD40L and cytokine mRNA expression.
320 11238201 Quantification of mRNA expression of CD40L, interleukin-4 (IL-4), IL-12p40, and gamma interferon (IFN-gamma) was performed by reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA)-PCR with resting and stimulated peripheral blood mononuclear cells.
321 11238201 The results showed a significant increase in the expression of mRNAs for CD40L and IL-4, but not IL-12p40 or IFN-gamma, in stimulated cultures from unimmunized individuals.
322 11238201 CD40L and IL-4 mRNA expression was significantly higher in postimmunization than in preimmunization samples stimulated with the individual pneumococcal serotypes.
323 11265774 Proinflammatory cytokines and CD40 ligand enhance cross-presentation and cross-priming capability of human dendritic cells internalizing apoptotic cancer cells.
324 11265774 Proinflammatory cytokines (PC), CD40 ligand (CD40L) and/or interferon-gamma (IFN-gamma) were found to markedly enhance the immunogenicity of TAA presented by DC.
325 11265774 While PC upregulated expression of major histocompatibility complex class I/II and costimulatory molecules on the surface of DC, CD40L +/- IFN-gamma increased interleukin (IL)- 12 and to a lesser extent, IL-15 production by DC.
326 11265774 Additionally, lactacystin, a specific proteasome inhibitor, significantly abrogated the effects of IFN-gamma and, in part, also those of CD40L or PC.
327 11265774 The ability of DC + ATC to cross-prime TAA-inexperienced ("naive") T cells was significantly enhanced by PC and CD40L or CD40L + IFN-gamma, but not by IFN-gamma alone.
328 11265774 These results indicate that future vaccines for patients with cancer incorporating DC fed with ATC could be made more effective by the addition of proinflammatory cytokines or CD40L +/- IFN-gamma to improve the DC function.
329 11265774 Proinflammatory cytokines and CD40 ligand enhance cross-presentation and cross-priming capability of human dendritic cells internalizing apoptotic cancer cells.
330 11265774 Proinflammatory cytokines (PC), CD40 ligand (CD40L) and/or interferon-gamma (IFN-gamma) were found to markedly enhance the immunogenicity of TAA presented by DC.
331 11265774 While PC upregulated expression of major histocompatibility complex class I/II and costimulatory molecules on the surface of DC, CD40L +/- IFN-gamma increased interleukin (IL)- 12 and to a lesser extent, IL-15 production by DC.
332 11265774 Additionally, lactacystin, a specific proteasome inhibitor, significantly abrogated the effects of IFN-gamma and, in part, also those of CD40L or PC.
333 11265774 The ability of DC + ATC to cross-prime TAA-inexperienced ("naive") T cells was significantly enhanced by PC and CD40L or CD40L + IFN-gamma, but not by IFN-gamma alone.
334 11265774 These results indicate that future vaccines for patients with cancer incorporating DC fed with ATC could be made more effective by the addition of proinflammatory cytokines or CD40L +/- IFN-gamma to improve the DC function.
335 11277614 Resiquimod, like CD40, stimulates antibody secretion, cytokine production, protection from apoptosis, and CD80 upregulation.
336 11290793 Intravenous immunization of C57BL/6 mice with heat-killed Listeria monocytogenes (HKL) induced minimal immunity, but HKL administered together with an agonistic anti-CD40 mAb induced high levels of both CD4(+) and CD8(+) T cells capable of producing IFN-gamma following in vitro HKL stimulation.
337 11290793 CD40-mediated adjuvant activity required endogenous IL-12 at the time of vaccination, and protection was mediated by both CD8(+) and CD4(+) T cells.
338 11290793 Thus, CD40 signaling can deliver potent adjuvant activity for vaccination against intracellular pathogens and is particularly effective for pathogens requiring both CD4(+) and CD8(+) T cells for effective control.
339 11290793 Intravenous immunization of C57BL/6 mice with heat-killed Listeria monocytogenes (HKL) induced minimal immunity, but HKL administered together with an agonistic anti-CD40 mAb induced high levels of both CD4(+) and CD8(+) T cells capable of producing IFN-gamma following in vitro HKL stimulation.
340 11290793 CD40-mediated adjuvant activity required endogenous IL-12 at the time of vaccination, and protection was mediated by both CD8(+) and CD4(+) T cells.
341 11290793 Thus, CD40 signaling can deliver potent adjuvant activity for vaccination against intracellular pathogens and is particularly effective for pathogens requiring both CD4(+) and CD8(+) T cells for effective control.
342 11290810 Targeting antigen in mature dendritic cells for simultaneous stimulation of CD4+ and CD8+ T cells.
343 11290810 Immature DC (DCimm) capture, process, and present Ags to CD4(+) lymphocytes, which reciprocally activate DCimm through CD40, and the resulting mature DC (DCmat) loose phagocytic capacity, but acquire the ability to efficiently stimulate CD8(+) lymphocytes.
344 11290810 Recombinant vaccinia viruses (rVV) provide a rapid, easy, and efficient method to introduce Ags into DC, but we observed that rVV infection of DCimm results in blockade of DC maturation in response to all activation signals, including CD40L, monocyte-conditioned medium, LPS, TNF-alpha, and poly(I:C), and failure to induce a CD8(+) response.
345 11290810 These results demonstrate that despite rVV interference with DCimm maturation, a single targeting vector can deliver Ags to DCmat for the effective simultaneous stimulation of both CD4(+) and CD8(+) cells.
346 11292748 Vaccination against the intracellular pathogens Leishmania major and L. amazonensis by directing CD40 ligand to macrophages.
347 11292748 CD40 ligand (CD40L) is a potent inducer of interleukin-12 (IL-12) production from macrophages and dendritic cells.
348 11292748 These studies suggest that CD40L could be exploited to improve vaccines against intracellular pathogens, especially those organisms that reside within cells expressing CD40 on their surface.
349 11292748 Vaccination against the intracellular pathogens Leishmania major and L. amazonensis by directing CD40 ligand to macrophages.
350 11292748 CD40 ligand (CD40L) is a potent inducer of interleukin-12 (IL-12) production from macrophages and dendritic cells.
351 11292748 These studies suggest that CD40L could be exploited to improve vaccines against intracellular pathogens, especially those organisms that reside within cells expressing CD40 on their surface.
352 11292748 Vaccination against the intracellular pathogens Leishmania major and L. amazonensis by directing CD40 ligand to macrophages.
353 11292748 CD40 ligand (CD40L) is a potent inducer of interleukin-12 (IL-12) production from macrophages and dendritic cells.
354 11292748 These studies suggest that CD40L could be exploited to improve vaccines against intracellular pathogens, especially those organisms that reside within cells expressing CD40 on their surface.
355 11348665 But CpG-ODN stimulation up-regulated the expression of MHC-I, MHC-II, CD40, ICAM-1 molecules in A20 cells, enhanced the antigen uptake ability of A20 cells, and promoted A20 cell production of IgM and IgG.
356 11380416 A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2.
357 11380416 In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vaccine of CD40-activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination.
358 11380416 CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants.
359 11380416 We demonstrated the safety and feasibility in combining autologous tumour-specific T-cell therapy with low-dose IL-2 and that clinical trials based on the use of CD40-activated autologous tumour cell vaccines are warranted in patients with CD40-activated autologous tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells.
360 11380416 A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2.
361 11380416 In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vaccine of CD40-activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination.
362 11380416 CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants.
363 11380416 We demonstrated the safety and feasibility in combining autologous tumour-specific T-cell therapy with low-dose IL-2 and that clinical trials based on the use of CD40-activated autologous tumour cell vaccines are warranted in patients with CD40-activated autologous tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells.
364 11380416 A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2.
365 11380416 In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vaccine of CD40-activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination.
366 11380416 CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants.
367 11380416 We demonstrated the safety and feasibility in combining autologous tumour-specific T-cell therapy with low-dose IL-2 and that clinical trials based on the use of CD40-activated autologous tumour cell vaccines are warranted in patients with CD40-activated autologous tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells.
368 11380416 A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2.
369 11380416 In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vaccine of CD40-activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination.
370 11380416 CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants.
371 11380416 We demonstrated the safety and feasibility in combining autologous tumour-specific T-cell therapy with low-dose IL-2 and that clinical trials based on the use of CD40-activated autologous tumour cell vaccines are warranted in patients with CD40-activated autologous tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells.
372 11399230 Modulation of cellular responses by plasmid CD40L: CD40L plasmid vectors enhance antigen-specific helper T cell type 1 CD4+ T cell-mediated protective immunity against herpes simplex virus type 2 in vivo.
373 11399230 The costimulatory molecule CD40, expressed on antigen-presenting cells, is thought to interact with CD40 ligand (CD40L) expressed on activated CD4(+) or CD8(+) T cells to further drive interleukin-2 receptor (IL-2R) expression and antigen-specific T cell expansion necessary for both class II and class I responses.
374 11399230 To compare the specific roles of these two costimulatory molecules in immune induction in a herpes simplex virus (HSV) model, we constructed plasmid DNAs expressing CD40 and CD40L, coimmunized these molecules with a gD plasmid vaccine, and then analyzed immune modulatory effects as well as protection against lethal HSV-2 challenge.
375 11399230 CD40L also enhanced Th cell proliferative responses and production of Th1-type cytokines (IL-2 and IFN-gamma) and beta-chemokines (RANTES and MIP-1alpha) from splenocytes.
376 11399230 When animals were challenged with a lethal dose of HSV-2, CD40L-coimmunized animals exhibited a significantly enhanced survival rate, as compared with CD40 coinjection or gD DNA vaccine alone.
377 11399230 CD40L also promoted migration of CD4(+) T cells into the muscle sites.
378 11399230 These studies demonstrate that CD40L can play an important role in protective antigen-specific immunity in a gene-based model system through increased expansion of the CD4(+) Th1 T cell subset in vivo.
379 11399230 Modulation of cellular responses by plasmid CD40L: CD40L plasmid vectors enhance antigen-specific helper T cell type 1 CD4+ T cell-mediated protective immunity against herpes simplex virus type 2 in vivo.
380 11399230 The costimulatory molecule CD40, expressed on antigen-presenting cells, is thought to interact with CD40 ligand (CD40L) expressed on activated CD4(+) or CD8(+) T cells to further drive interleukin-2 receptor (IL-2R) expression and antigen-specific T cell expansion necessary for both class II and class I responses.
381 11399230 To compare the specific roles of these two costimulatory molecules in immune induction in a herpes simplex virus (HSV) model, we constructed plasmid DNAs expressing CD40 and CD40L, coimmunized these molecules with a gD plasmid vaccine, and then analyzed immune modulatory effects as well as protection against lethal HSV-2 challenge.
382 11399230 CD40L also enhanced Th cell proliferative responses and production of Th1-type cytokines (IL-2 and IFN-gamma) and beta-chemokines (RANTES and MIP-1alpha) from splenocytes.
383 11399230 When animals were challenged with a lethal dose of HSV-2, CD40L-coimmunized animals exhibited a significantly enhanced survival rate, as compared with CD40 coinjection or gD DNA vaccine alone.
384 11399230 CD40L also promoted migration of CD4(+) T cells into the muscle sites.
385 11399230 These studies demonstrate that CD40L can play an important role in protective antigen-specific immunity in a gene-based model system through increased expansion of the CD4(+) Th1 T cell subset in vivo.
386 11399230 Modulation of cellular responses by plasmid CD40L: CD40L plasmid vectors enhance antigen-specific helper T cell type 1 CD4+ T cell-mediated protective immunity against herpes simplex virus type 2 in vivo.
387 11399230 The costimulatory molecule CD40, expressed on antigen-presenting cells, is thought to interact with CD40 ligand (CD40L) expressed on activated CD4(+) or CD8(+) T cells to further drive interleukin-2 receptor (IL-2R) expression and antigen-specific T cell expansion necessary for both class II and class I responses.
388 11399230 To compare the specific roles of these two costimulatory molecules in immune induction in a herpes simplex virus (HSV) model, we constructed plasmid DNAs expressing CD40 and CD40L, coimmunized these molecules with a gD plasmid vaccine, and then analyzed immune modulatory effects as well as protection against lethal HSV-2 challenge.
389 11399230 CD40L also enhanced Th cell proliferative responses and production of Th1-type cytokines (IL-2 and IFN-gamma) and beta-chemokines (RANTES and MIP-1alpha) from splenocytes.
390 11399230 When animals were challenged with a lethal dose of HSV-2, CD40L-coimmunized animals exhibited a significantly enhanced survival rate, as compared with CD40 coinjection or gD DNA vaccine alone.
391 11399230 CD40L also promoted migration of CD4(+) T cells into the muscle sites.
392 11399230 These studies demonstrate that CD40L can play an important role in protective antigen-specific immunity in a gene-based model system through increased expansion of the CD4(+) Th1 T cell subset in vivo.
393 11403919 We studied strategies for the reliable generation of such a tumor vaccine by functional maturation of DCs via interaction of CD40 with its ligand (CD40L, CD154).
394 11403919 Exposure of immature DCs to CD40L transgenic cells, soluble recombinant human CD40L molecules or lipopolysaccharide induced expression of the co-stimulatory molecules, CD80 and CD86, and supported an allogeneic mixed leukocyte reaction.
395 11403919 In contrast, the release of IL-12, an important mediator of anti-tumor immunity, and antigen-specific expansion and IFNgamma secretion of lymphocytes, was strongly triggered only by DCs exposed to CD40L transgenic cells.
396 11440619 Cross-strain protection against clinical and laboratory strains of Pseudomonas aeruginosa mediated by dendritic cells genetically modified to express CD40 ligand and pulsed with specific strains of Pseudomonas aeruginosa.
397 11440619 We have shown that dendritic cells (DCs) genetically engineered with a recombinant adenovirus vector (Ad) to express CD40 ligand (CD40L) elicit specific humoral immunity against the Pseudomonas aeruginosa laboratory strain PAO1, without CD4(+) T cell help.
398 11440619 Cross-strain protection against clinical and laboratory strains of Pseudomonas aeruginosa mediated by dendritic cells genetically modified to express CD40 ligand and pulsed with specific strains of Pseudomonas aeruginosa.
399 11440619 We have shown that dendritic cells (DCs) genetically engineered with a recombinant adenovirus vector (Ad) to express CD40 ligand (CD40L) elicit specific humoral immunity against the Pseudomonas aeruginosa laboratory strain PAO1, without CD4(+) T cell help.
400 11449073 Proinflammatory Cytokines and CD40 Ligand Enhance Cross-Presentation and Cross-Priming Capability of Human Dendritic Cells Internalizing Apoptotic Cancer Cells.
401 11449073 Proinflammatory cytokines (PC), CD40 ligand (CD40L) and/or interferon-gamma (IFN-gamma) were found to markedly enhance the immunogenicity of TAA presented by DC.
402 11449073 While PC upregulated expression of major histocompatibility complex class I/II and costimulatory molecules on the surface of DC, CD40L +/- IFN-gamma increased interleukin (IL)-12 and to a lesser extent, IL-15 production by DC.
403 11449073 Additionally, lactacystin, a specific proteasome inhibitor, significantly abrogated the effects of IFN-gamma and, in part, also those of CD40L or PC.
404 11449073 The ability of DC + ATC to cross-prime TAA-inexperienced ("naive") T cells was significantly enhanced by PC and CD40L or CD40L + IFN-gamma, but not by IFN-gamma alone.
405 11449073 These results indicate that future vaccines for patients with cancer incorporating DC fed with ATC could be made more effective by the addition of proinflammatory cytokines or CD40L +/- IFN-gamma to improve the DC function.
406 11449073 Proinflammatory Cytokines and CD40 Ligand Enhance Cross-Presentation and Cross-Priming Capability of Human Dendritic Cells Internalizing Apoptotic Cancer Cells.
407 11449073 Proinflammatory cytokines (PC), CD40 ligand (CD40L) and/or interferon-gamma (IFN-gamma) were found to markedly enhance the immunogenicity of TAA presented by DC.
408 11449073 While PC upregulated expression of major histocompatibility complex class I/II and costimulatory molecules on the surface of DC, CD40L +/- IFN-gamma increased interleukin (IL)-12 and to a lesser extent, IL-15 production by DC.
409 11449073 Additionally, lactacystin, a specific proteasome inhibitor, significantly abrogated the effects of IFN-gamma and, in part, also those of CD40L or PC.
410 11449073 The ability of DC + ATC to cross-prime TAA-inexperienced ("naive") T cells was significantly enhanced by PC and CD40L or CD40L + IFN-gamma, but not by IFN-gamma alone.
411 11449073 These results indicate that future vaccines for patients with cancer incorporating DC fed with ATC could be made more effective by the addition of proinflammatory cytokines or CD40L +/- IFN-gamma to improve the DC function.
412 11468146 Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.
413 11468146 This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC.
414 11468146 Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC.
415 11468146 More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells.
416 11468146 Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.
417 11468146 This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC.
418 11468146 Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC.
419 11468146 More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells.
420 11468146 Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.
421 11468146 This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC.
422 11468146 Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC.
423 11468146 More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells.
424 11477458 Transgenic expression of CD40L and interleukin-2 induces an autologous antitumor immune response in patients with non-Hodgkin's lymphoma.
425 11477458 To stimulate NHL-specific immune responses, we attempted to transfer the human CD40 ligand (hCD40L) gene to B-NHL cells and enhance their co-stimulatory potential.
426 11477458 Expression of transgenic human CD40L on these CD40-positive cells was in turn associated with up-regulation of other co-stimulatory molecules including B7-1/-2.
427 11477458 These findings suggest that the combination of CD40L and IL2 gene-modified B-NHL cells will induce a cytotoxic immune response in vivo directed against unmodified tumor cells.
428 11477458 Transgenic expression of CD40L and interleukin-2 induces an autologous antitumor immune response in patients with non-Hodgkin's lymphoma.
429 11477458 To stimulate NHL-specific immune responses, we attempted to transfer the human CD40 ligand (hCD40L) gene to B-NHL cells and enhance their co-stimulatory potential.
430 11477458 Expression of transgenic human CD40L on these CD40-positive cells was in turn associated with up-regulation of other co-stimulatory molecules including B7-1/-2.
431 11477458 These findings suggest that the combination of CD40L and IL2 gene-modified B-NHL cells will induce a cytotoxic immune response in vivo directed against unmodified tumor cells.
432 11477558 Our data showed that phagocytosis of apoptotic/necrotic tumor cells resulted in maturation of DCs with up-regulated expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor], chemokines (MIP-1alpha, MIP-1beta and MIP-2), the CC chemokine receptor CCR7 and the cell surface molecules (MHC class II, CD11b, CD40 and CD86), and down-regulated expression of the CC chemokine receptors CCR2 and CCR5.
433 11498762 Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-gamma gene into lung cancer.
434 11498762 Immunohistochemical study showed that inflammatory cells, including CD4+, CD8+ T cells and NK cells, infiltrated into the inoculated 3LLSA-CD40L tumor tissue.
435 11498762 These results indicate that the in vivo priming with CD40L- and IFN-gamma gene-transduced lung cancer cells is a promising strategy for inducing antitumor immunity in the treatment of lung cancer.
436 11500820 In this report OMPC is shown to enhance CD40 ligand-mediated, T cell-dependent antibody production in mice.
437 11500820 This paralleled the induction by OMPC of CD86, CD80 and CD40 costimulatory molecules on human neonatal and murine B cells and of Th1 cytokines.
438 11500820 In this report OMPC is shown to enhance CD40 ligand-mediated, T cell-dependent antibody production in mice.
439 11500820 This paralleled the induction by OMPC of CD86, CD80 and CD40 costimulatory molecules on human neonatal and murine B cells and of Th1 cytokines.
440 11529939 We found that Murabutide triggers immunophenotypic changes as upon treatment, iDCs up-regulate the surface expression of the major histocompatibility complex type II molecule human leucocyte antigen-DR, the co-stimulatory molecules CD80, CD86 and CD40 and the differentiation marker CD83, and down-regulate the expression of the mannose receptor.
441 11529939 Furthermore, in the presence of Murabutide, DCs transiently increased the release of macrophage inhibitory protein-1 beta, tumour necrosis factor-alpha and interleukin-10, whereas the enhanced production of macrophage-colony stimulating factor was sustained over the 3-day period analysed.
442 11533211 The presented data demonstrate that recombinant AAV (rAAV) can efficiently transduce MOs as well as DCs generated by MO culture with granulocyte-macrophage colony-stimulating factor plus interleukin in vitro. rAAV transgene expression in MO-derived DCs could be enhanced by etoposide, previously reported to enhance AAV gene expression. rAAV transduction of freshly purified MO followed by 7 days of culture with cytokines to generate DCs, and subsequent sorting for coexpression of DC markers CD1a and CD40, showed robust transgene expression as well as evidence of nuclear localization of the rAAV genome in the DC population.
443 11591784 A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice.
444 11591784 A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic cells.
445 11591784 Peripheral T cell tolerance to CEA was broken in a prophylactic model by this novel, dual-function DNA vaccine, whose efficacy was further enhanced by boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2).
446 11591784 Second, specific activation of dendritic cells was indicated by their marked up-regulation in expression of costimulatory molecules B7.1 (CD80), B7.2 (CD86), and ICAM-1.
447 11591784 Third, a decisive increase over control values was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma and IL-12.
448 11591784 Fourth, activation of CTLs was augmented, as indicated by up-regulation of activity markers LFA-1, CD25, CD28, and CD69.
449 11591784 Taken together, these results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand trimer combined with tumor-targeted IL-2 may be a promising strategy for the rational development of DNA-based cancer vaccines for future clinical applications.
450 11591784 A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice.
451 11591784 A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic cells.
452 11591784 Peripheral T cell tolerance to CEA was broken in a prophylactic model by this novel, dual-function DNA vaccine, whose efficacy was further enhanced by boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2).
453 11591784 Second, specific activation of dendritic cells was indicated by their marked up-regulation in expression of costimulatory molecules B7.1 (CD80), B7.2 (CD86), and ICAM-1.
454 11591784 Third, a decisive increase over control values was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma and IL-12.
455 11591784 Fourth, activation of CTLs was augmented, as indicated by up-regulation of activity markers LFA-1, CD25, CD28, and CD69.
456 11591784 Taken together, these results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand trimer combined with tumor-targeted IL-2 may be a promising strategy for the rational development of DNA-based cancer vaccines for future clinical applications.
457 11591784 A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice.
458 11591784 A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic cells.
459 11591784 Peripheral T cell tolerance to CEA was broken in a prophylactic model by this novel, dual-function DNA vaccine, whose efficacy was further enhanced by boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2).
460 11591784 Second, specific activation of dendritic cells was indicated by their marked up-regulation in expression of costimulatory molecules B7.1 (CD80), B7.2 (CD86), and ICAM-1.
461 11591784 Third, a decisive increase over control values was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma and IL-12.
462 11591784 Fourth, activation of CTLs was augmented, as indicated by up-regulation of activity markers LFA-1, CD25, CD28, and CD69.
463 11591784 Taken together, these results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand trimer combined with tumor-targeted IL-2 may be a promising strategy for the rational development of DNA-based cancer vaccines for future clinical applications.
464 11672594 In particular, the potential involvement of: (i) the CpG pattern-recognition receptor, toll-like receptor-9; (ii) the dendritic cell-specific surface adhesion molecule, DC-SIGN; and (iii) the molecular interactions between CD40 and CD154 in the evolution of protective cell-mediated immunity to DNA vaccines are discussed.
465 11691812 Flow cytometric analysis indicated enhanced expression of MHC class I and II molecules as well as CD80, CD86, CD40, and CD54, and reverse transcription-PCR analysis revealed increased levels of interleukin 12 p40 mRNA.
466 11691813 Significant inhibition of established lung metastases required immunization with peptide-pulsed DCs pretreated with CD40 ligand that has been demonstrated to increase the T-cell stimulatory activity of DCs.
467 11698440 CD40 ligand promotes priming of fully potent antitumor CD4(+) T cells in draining lymph nodes in the presence of apoptotic tumor cells.
468 11698440 It has been demonstrated that interactions of CD40-CD40 ligand can replace CD4(+) T cell help and enable dendritic cells to prime cytotoxic T cells.
469 11698440 Here, we demonstrate that antitumor reactivity induced in regional lymph nodes (LNs) by s.c. injection of CD40 ligand (CD40L)-transduced tumor (MCA205 CD40L) showed far superior therapeutic efficacy against established brain tumors of a weakly immunogenic fibrosarcoma, MCA205, when adoptively transferred.
470 11698440 In contrast, T cells derived from LNs immunized without MCA205 CD40L required ex vivo anti-CD3/IL-2 activation to elicit therapeutic activity.
471 11698440 On anti-CD3/IL-2 activation, cells from LNs immunized with MCA205 CD40L exhibited superior per cell antitumor reactivity.
472 11698440 An in vitro depletion study revealed that either CD4(+) or CD8(+) T cells could mediate therapeutic efficacy but that the antitumor efficacy mediated by CD4(+) T cells was far superior.
473 11698440 Cytosolic flow cytometric analyses indicated that priming of CD4(+) cells in LNs draining CD40L-expressing tumors was polarized to the Th1 type.
474 11698440 This is the first report that fully potent antitumor CD4(+) T cell priming was promoted by s.c. injection of CD40L-transduced tumor in the presence of apoptotic tumor cells.
475 11698440 CD40 ligand promotes priming of fully potent antitumor CD4(+) T cells in draining lymph nodes in the presence of apoptotic tumor cells.
476 11698440 It has been demonstrated that interactions of CD40-CD40 ligand can replace CD4(+) T cell help and enable dendritic cells to prime cytotoxic T cells.
477 11698440 Here, we demonstrate that antitumor reactivity induced in regional lymph nodes (LNs) by s.c. injection of CD40 ligand (CD40L)-transduced tumor (MCA205 CD40L) showed far superior therapeutic efficacy against established brain tumors of a weakly immunogenic fibrosarcoma, MCA205, when adoptively transferred.
478 11698440 In contrast, T cells derived from LNs immunized without MCA205 CD40L required ex vivo anti-CD3/IL-2 activation to elicit therapeutic activity.
479 11698440 On anti-CD3/IL-2 activation, cells from LNs immunized with MCA205 CD40L exhibited superior per cell antitumor reactivity.
480 11698440 An in vitro depletion study revealed that either CD4(+) or CD8(+) T cells could mediate therapeutic efficacy but that the antitumor efficacy mediated by CD4(+) T cells was far superior.
481 11698440 Cytosolic flow cytometric analyses indicated that priming of CD4(+) cells in LNs draining CD40L-expressing tumors was polarized to the Th1 type.
482 11698440 This is the first report that fully potent antitumor CD4(+) T cell priming was promoted by s.c. injection of CD40L-transduced tumor in the presence of apoptotic tumor cells.
483 11714738 Here, we demonstrate that bone marrow-derived dendritic cells (DCs) expressing the murine CD40 ligand, when pulsed ex vivo by PC antigen, elicited significant titers of anti-PC IgG in CD4-deficient mice.
484 11714787 Lipopolysaccharide modulation of dendritic cells is insufficient to mature dendritic cells to generate CTLs from naive polyclonal CD8+ T cells in vitro, whereas CD40 ligation is essential.
485 11714787 Many cytotoxic CD8+ T cell responses are dependent on the interactions between CD40 ligand on the helper CD4+ T cell and CD40 on the APC.
486 11714787 Although CD40 triggering of dendritic cells (DC) has been shown to mature the DC by increasing the level of expression of costimulatory molecules and inducing IL-12 secretion, the precise mechanisms by which CD40-CD40 ligand interactions allow DC to drive CTL responses remain unknown.
487 11714787 We have used an in vitro model in which naive polyclonal CD8+ T cells can be activated by bone marrow-derived DC to investigate factor(s) that are responsible for this CD40-dependent generation of CTLs.
488 11714787 Lipopolysaccharide modulation of dendritic cells is insufficient to mature dendritic cells to generate CTLs from naive polyclonal CD8+ T cells in vitro, whereas CD40 ligation is essential.
489 11714787 Many cytotoxic CD8+ T cell responses are dependent on the interactions between CD40 ligand on the helper CD4+ T cell and CD40 on the APC.
490 11714787 Although CD40 triggering of dendritic cells (DC) has been shown to mature the DC by increasing the level of expression of costimulatory molecules and inducing IL-12 secretion, the precise mechanisms by which CD40-CD40 ligand interactions allow DC to drive CTL responses remain unknown.
491 11714787 We have used an in vitro model in which naive polyclonal CD8+ T cells can be activated by bone marrow-derived DC to investigate factor(s) that are responsible for this CD40-dependent generation of CTLs.
492 11714787 Lipopolysaccharide modulation of dendritic cells is insufficient to mature dendritic cells to generate CTLs from naive polyclonal CD8+ T cells in vitro, whereas CD40 ligation is essential.
493 11714787 Many cytotoxic CD8+ T cell responses are dependent on the interactions between CD40 ligand on the helper CD4+ T cell and CD40 on the APC.
494 11714787 Although CD40 triggering of dendritic cells (DC) has been shown to mature the DC by increasing the level of expression of costimulatory molecules and inducing IL-12 secretion, the precise mechanisms by which CD40-CD40 ligand interactions allow DC to drive CTL responses remain unknown.
495 11714787 We have used an in vitro model in which naive polyclonal CD8+ T cells can be activated by bone marrow-derived DC to investigate factor(s) that are responsible for this CD40-dependent generation of CTLs.
496 11714787 Lipopolysaccharide modulation of dendritic cells is insufficient to mature dendritic cells to generate CTLs from naive polyclonal CD8+ T cells in vitro, whereas CD40 ligation is essential.
497 11714787 Many cytotoxic CD8+ T cell responses are dependent on the interactions between CD40 ligand on the helper CD4+ T cell and CD40 on the APC.
498 11714787 Although CD40 triggering of dendritic cells (DC) has been shown to mature the DC by increasing the level of expression of costimulatory molecules and inducing IL-12 secretion, the precise mechanisms by which CD40-CD40 ligand interactions allow DC to drive CTL responses remain unknown.
499 11714787 We have used an in vitro model in which naive polyclonal CD8+ T cells can be activated by bone marrow-derived DC to investigate factor(s) that are responsible for this CD40-dependent generation of CTLs.
500 11730853 CD40 ligand and lipopolysaccharide enhance the in vitro generation of melanoma-reactive T-cells.
501 11730853 We have developed an efficient and reproducible method for detecting tumor-specific T cells by optimizing the activation of antigen presenting cells (APC) in peripheral blood mononuclear cells (PBMC) of metastatic melanoma patients with soluble trimeric CD40-ligand (CD40L) or lipopolysaccharide (LPS).
502 11730853 This method significantly improved the generation of Melan-A/MART-1:27-35 and Melan-A/MART-1:26-35(27L) peptide/tumor-specific cells as well as lower frequency tyrosinase:368-376(370D) specific T cells from the PBMC of melanoma patients.
503 11730853 Additionally, PBMC activation improved the detection of tumor-specific precursors from melanoma patients previously immunized with peptides derived from Melan-A/MART-1, tyrosinase and gp100.
504 11730853 CD40 ligand and lipopolysaccharide enhance the in vitro generation of melanoma-reactive T-cells.
505 11730853 We have developed an efficient and reproducible method for detecting tumor-specific T cells by optimizing the activation of antigen presenting cells (APC) in peripheral blood mononuclear cells (PBMC) of metastatic melanoma patients with soluble trimeric CD40-ligand (CD40L) or lipopolysaccharide (LPS).
506 11730853 This method significantly improved the generation of Melan-A/MART-1:27-35 and Melan-A/MART-1:26-35(27L) peptide/tumor-specific cells as well as lower frequency tyrosinase:368-376(370D) specific T cells from the PBMC of melanoma patients.
507 11730853 Additionally, PBMC activation improved the detection of tumor-specific precursors from melanoma patients previously immunized with peptides derived from Melan-A/MART-1, tyrosinase and gp100.
508 11751948 Requirement for NK cells in CD40 ligand-mediated rejection of Philadelphia chromosome-positive acute lymphoblastic leukemia cells.
509 11751948 We are studying the potential to elicit autologous antileukemic immune responses by introducing genes encoding immunomodulators (CD40 ligand (CD40L), CD80, and GM-CSF) into leukemia cells.
510 11751948 BM185 cells expressing CD40L or CD80 alone, when injected into BALB/c mice, were rejected in approximately 25% of mice, whereas cohorts receiving BM185 cells expressing two or more immunomodulator genes rejected challenge 50-76% of the time.
511 11751948 Addition of murine rIL-12 treatments in conjunction with BM185/CD80/CD40L/GM-CSF vaccination allowed rejection of preestablished leukemia.
512 11751948 BM185 cell lines expressing CD40L were rejected in BALB/c nu/nu (nude) mice, in contrast to cell lines expressing CD80 and/or GM-CSF.
513 11751948 Requirement for NK cells in CD40 ligand-mediated rejection of Philadelphia chromosome-positive acute lymphoblastic leukemia cells.
514 11751948 We are studying the potential to elicit autologous antileukemic immune responses by introducing genes encoding immunomodulators (CD40 ligand (CD40L), CD80, and GM-CSF) into leukemia cells.
515 11751948 BM185 cells expressing CD40L or CD80 alone, when injected into BALB/c mice, were rejected in approximately 25% of mice, whereas cohorts receiving BM185 cells expressing two or more immunomodulator genes rejected challenge 50-76% of the time.
516 11751948 Addition of murine rIL-12 treatments in conjunction with BM185/CD80/CD40L/GM-CSF vaccination allowed rejection of preestablished leukemia.
517 11751948 BM185 cell lines expressing CD40L were rejected in BALB/c nu/nu (nude) mice, in contrast to cell lines expressing CD80 and/or GM-CSF.
518 11777991 Maturation parameters such as production of IL-12 and increases in cell surface expression of HLA-DR, CD80, CD86, CD40, and CD83 were observed following DC treatment with MPL.
519 11777991 This is likely to be related to differences in the kinetics of extracellular signal-related kinase 1/2 and p-38 phosphorylation induced by both molecules.
520 11777991 The observed effect was related to the fact that MPL also acts directly on T cells, likely through their Toll-like receptors, by increasing their intracellular calcium and up-regulating their CD40 ligand expression.
521 11777991 Maturation parameters such as production of IL-12 and increases in cell surface expression of HLA-DR, CD80, CD86, CD40, and CD83 were observed following DC treatment with MPL.
522 11777991 This is likely to be related to differences in the kinetics of extracellular signal-related kinase 1/2 and p-38 phosphorylation induced by both molecules.
523 11777991 The observed effect was related to the fact that MPL also acts directly on T cells, likely through their Toll-like receptors, by increasing their intracellular calcium and up-regulating their CD40 ligand expression.
524 11781244 Infection induced DC morphology and altered the expression of surface markers, including loss of CD14, de novo induction of CD83 and CD25, and strongly augmented expression of CD86, CD80, CD40, and HLA-DR and HLA class I molecules.
525 11792391 Characteristic immunophenotypic and functional DC maturation induced by standard monocyte conditioned medium (MCM) was compared to the activation induced by a panel of stimuli including soluble CD40L, LPS, Poly I:C, PGE(2)/TNFalpha, and a cocktail mixture of PGE(2)/TNFalpha/IL-1beta/IL-6.
526 11792391 Immunophenotypic analysis confirmed that all stimuli induced stable up-regulation of CD25, CD40, CD80, CD83, CD86, HLA-DR, DC-LAMP (CD208), and DEC-205 (CD205).
527 11797392 Formation of tri-molecular complex among T cell antigen receptor(TCR), major histocompatibility complex(MHC) molecule, and antigen peptide produces signal 1 via TCR.
528 11797392 However, signal 2 is elicited by interaction between CD28 and its ligands(CD80 and CD86) and is antigen-independent.
529 11797392 Interestingly, cell surface expression of CD80 and CD86 on antigen-presenting cell(APC) is regulated by stimulus via CD40.
530 11857039 Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8(+) cytotoxic T-cell activation and antitumor immunity.
531 11857039 CD40L, the ligand for CD40 on dendritic cells (DCs), plays an important role in their activation and is essential for induction of antigen-specific T-cell responses.
532 11857039 Our data show that transfection of DCs with recombinant adenovirus AdV-CD40L resulted in activation of DCs with up-regulated expression of proinflammatory cytokines (IL-1beta and IL-12), chemokines (RANTES, IP-10, and MIP-1alpha), and immunologically important cell surface molecules (CD54, CD80, and CD86).
533 11857039 Our data also demonstrate that DCs transfected with AdV-CD40L (DC(CD40L)) are able to stimulate enhanced allogeneic T-cell proliferation and Mut1-specific CD8(+) cytotoxic T-cell responses in vitro.
534 11857039 Thus, DCs engineered to express CD40L by adenovirus-mediated CD40 ligand gene transfer may offer a new strategy in production of DC cancer vaccines.
535 11857039 Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8(+) cytotoxic T-cell activation and antitumor immunity.
536 11857039 CD40L, the ligand for CD40 on dendritic cells (DCs), plays an important role in their activation and is essential for induction of antigen-specific T-cell responses.
537 11857039 Our data show that transfection of DCs with recombinant adenovirus AdV-CD40L resulted in activation of DCs with up-regulated expression of proinflammatory cytokines (IL-1beta and IL-12), chemokines (RANTES, IP-10, and MIP-1alpha), and immunologically important cell surface molecules (CD54, CD80, and CD86).
538 11857039 Our data also demonstrate that DCs transfected with AdV-CD40L (DC(CD40L)) are able to stimulate enhanced allogeneic T-cell proliferation and Mut1-specific CD8(+) cytotoxic T-cell responses in vitro.
539 11857039 Thus, DCs engineered to express CD40L by adenovirus-mediated CD40 ligand gene transfer may offer a new strategy in production of DC cancer vaccines.
540 11857039 Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8(+) cytotoxic T-cell activation and antitumor immunity.
541 11857039 CD40L, the ligand for CD40 on dendritic cells (DCs), plays an important role in their activation and is essential for induction of antigen-specific T-cell responses.
542 11857039 Our data show that transfection of DCs with recombinant adenovirus AdV-CD40L resulted in activation of DCs with up-regulated expression of proinflammatory cytokines (IL-1beta and IL-12), chemokines (RANTES, IP-10, and MIP-1alpha), and immunologically important cell surface molecules (CD54, CD80, and CD86).
543 11857039 Our data also demonstrate that DCs transfected with AdV-CD40L (DC(CD40L)) are able to stimulate enhanced allogeneic T-cell proliferation and Mut1-specific CD8(+) cytotoxic T-cell responses in vitro.
544 11857039 Thus, DCs engineered to express CD40L by adenovirus-mediated CD40 ligand gene transfer may offer a new strategy in production of DC cancer vaccines.
545 11857387 The results indicate that PMV modified by engraftment of recombinant forms of B7.1 and CD40 and incorporation of IL-2 can be used to modulate immune responses, which provides a novel approach for the development of anti-tumor vaccines and cancer immunotherapies.
546 11884445 Essential role for CD40 ligand interactions in T lymphocyte-mediated modulation of the murine immune response to pneumococcal capsular polysaccharides.
547 11884445 We investigated whether CD40 ligand (CD40L) plays a role in T lymphocyte-mediated regulation of the immune response to caps-PS, which are considered thymus-independent Ags.
548 11884445 Blocking CD40L in vitro decreased the IgM response to caps-PS and abolished the helper effect of CD4(+) T lymphocytes.
549 11884445 CD4(+) T lymphocyte-depleted murine spleen cells, leaving a B and CD8(+) T lymphocyte fraction, elicited only a weak in vivo and in vitro Ab response, which was enhanced after MR1 administration.
550 11884445 Essential role for CD40 ligand interactions in T lymphocyte-mediated modulation of the murine immune response to pneumococcal capsular polysaccharides.
551 11884445 We investigated whether CD40 ligand (CD40L) plays a role in T lymphocyte-mediated regulation of the immune response to caps-PS, which are considered thymus-independent Ags.
552 11884445 Blocking CD40L in vitro decreased the IgM response to caps-PS and abolished the helper effect of CD4(+) T lymphocytes.
553 11884445 CD4(+) T lymphocyte-depleted murine spleen cells, leaving a B and CD8(+) T lymphocyte fraction, elicited only a weak in vivo and in vitro Ab response, which was enhanced after MR1 administration.
554 11904731 DC were generated from peripheral mononuclear cells by co-cultivation with granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4).
555 11904731 After the cells had been pulsed with tumor antigens and co-cultured with autologous lymphocytes, the production of interferon-gamma (IFN-gamma) and IL-12 was analyzed, and lymphocyte proliferative response and cytotoxicity against the target tumor cell line were assessed.
556 11904731 CD83, CD86, HLA-DR, CD11c and CD40).
557 11911421 CD40 ligand immunotherapy in cancer: an efficient approach.
558 11911421 This review will discuss current anti-cancer immunotherapy; interleukin-2 therapy, tumor vaccine secreting Granulocyte macrophage-colony stimulating factor, dendritic cells fused with tumor cells, and CD40 ligand immunotherapy.
559 11911421 Moreover, we introduce our two kinds of CD40 ligand immuno-genetherapy; (1) oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium (published in BLOOD 2000), (2) cancer vaccine transfected with CD40 ligand ex vivo for neuroblastoma (unpublished).
560 11911421 CD40 ligand immunotherapy in cancer: an efficient approach.
561 11911421 This review will discuss current anti-cancer immunotherapy; interleukin-2 therapy, tumor vaccine secreting Granulocyte macrophage-colony stimulating factor, dendritic cells fused with tumor cells, and CD40 ligand immunotherapy.
562 11911421 Moreover, we introduce our two kinds of CD40 ligand immuno-genetherapy; (1) oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium (published in BLOOD 2000), (2) cancer vaccine transfected with CD40 ligand ex vivo for neuroblastoma (unpublished).
563 11911421 CD40 ligand immunotherapy in cancer: an efficient approach.
564 11911421 This review will discuss current anti-cancer immunotherapy; interleukin-2 therapy, tumor vaccine secreting Granulocyte macrophage-colony stimulating factor, dendritic cells fused with tumor cells, and CD40 ligand immunotherapy.
565 11911421 Moreover, we introduce our two kinds of CD40 ligand immuno-genetherapy; (1) oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium (published in BLOOD 2000), (2) cancer vaccine transfected with CD40 ligand ex vivo for neuroblastoma (unpublished).
566 11915168 Antitumor immune responses derived from transgenic expression of CD40 ligand in myeloma cells.
567 11915168 In the present study, we engineered a mouse myeloma cell line J558 with a cloned CD40 ligand (CD40L) gene.
568 11915168 We demonstrated that (i) the engineered J558/CD40L tumor cells expressing the CD40 ligand molecule lost their tumorigenicity in syngeneic mice, and (ii) the inoculation of J558/CD40L tumor cells further lead to the protective immunity against wild-type J558 tumors.
569 11915168 In animal studies using T-cell subset depleted mice, we further showed that the primary rejection of J558/CD40L tumors did not require T cells, but was mainly mediated by NK cells, whereas the effector phase of the protective immunity is mediated by CD8+ T cells.
570 11915168 In addition, our data, for the first time, showed that the inoculation of engineered J558/CD40L tumor cells is able to stimulate stronger activation of dendritic cells with enhanced expression of B7-1 and ICAM-1 molecules than the wild-type J558 tumor cells Taken together, we demonstrated the antitumor effect of engineered J558/CD40L tumor cells that is mediated by the activation of the host dendritic cells in vivo.
571 11915168 Our data indicate that the introduction of co-stimulatory CD40 ligand molecule will be useful as a new strategy of immunogene therapy against tumors.
572 11915168 Antitumor immune responses derived from transgenic expression of CD40 ligand in myeloma cells.
573 11915168 In the present study, we engineered a mouse myeloma cell line J558 with a cloned CD40 ligand (CD40L) gene.
574 11915168 We demonstrated that (i) the engineered J558/CD40L tumor cells expressing the CD40 ligand molecule lost their tumorigenicity in syngeneic mice, and (ii) the inoculation of J558/CD40L tumor cells further lead to the protective immunity against wild-type J558 tumors.
575 11915168 In animal studies using T-cell subset depleted mice, we further showed that the primary rejection of J558/CD40L tumors did not require T cells, but was mainly mediated by NK cells, whereas the effector phase of the protective immunity is mediated by CD8+ T cells.
576 11915168 In addition, our data, for the first time, showed that the inoculation of engineered J558/CD40L tumor cells is able to stimulate stronger activation of dendritic cells with enhanced expression of B7-1 and ICAM-1 molecules than the wild-type J558 tumor cells Taken together, we demonstrated the antitumor effect of engineered J558/CD40L tumor cells that is mediated by the activation of the host dendritic cells in vivo.
577 11915168 Our data indicate that the introduction of co-stimulatory CD40 ligand molecule will be useful as a new strategy of immunogene therapy against tumors.
578 11915168 Antitumor immune responses derived from transgenic expression of CD40 ligand in myeloma cells.
579 11915168 In the present study, we engineered a mouse myeloma cell line J558 with a cloned CD40 ligand (CD40L) gene.
580 11915168 We demonstrated that (i) the engineered J558/CD40L tumor cells expressing the CD40 ligand molecule lost their tumorigenicity in syngeneic mice, and (ii) the inoculation of J558/CD40L tumor cells further lead to the protective immunity against wild-type J558 tumors.
581 11915168 In animal studies using T-cell subset depleted mice, we further showed that the primary rejection of J558/CD40L tumors did not require T cells, but was mainly mediated by NK cells, whereas the effector phase of the protective immunity is mediated by CD8+ T cells.
582 11915168 In addition, our data, for the first time, showed that the inoculation of engineered J558/CD40L tumor cells is able to stimulate stronger activation of dendritic cells with enhanced expression of B7-1 and ICAM-1 molecules than the wild-type J558 tumor cells Taken together, we demonstrated the antitumor effect of engineered J558/CD40L tumor cells that is mediated by the activation of the host dendritic cells in vivo.
583 11915168 Our data indicate that the introduction of co-stimulatory CD40 ligand molecule will be useful as a new strategy of immunogene therapy against tumors.
584 11915168 Antitumor immune responses derived from transgenic expression of CD40 ligand in myeloma cells.
585 11915168 In the present study, we engineered a mouse myeloma cell line J558 with a cloned CD40 ligand (CD40L) gene.
586 11915168 We demonstrated that (i) the engineered J558/CD40L tumor cells expressing the CD40 ligand molecule lost their tumorigenicity in syngeneic mice, and (ii) the inoculation of J558/CD40L tumor cells further lead to the protective immunity against wild-type J558 tumors.
587 11915168 In animal studies using T-cell subset depleted mice, we further showed that the primary rejection of J558/CD40L tumors did not require T cells, but was mainly mediated by NK cells, whereas the effector phase of the protective immunity is mediated by CD8+ T cells.
588 11915168 In addition, our data, for the first time, showed that the inoculation of engineered J558/CD40L tumor cells is able to stimulate stronger activation of dendritic cells with enhanced expression of B7-1 and ICAM-1 molecules than the wild-type J558 tumor cells Taken together, we demonstrated the antitumor effect of engineered J558/CD40L tumor cells that is mediated by the activation of the host dendritic cells in vivo.
589 11915168 Our data indicate that the introduction of co-stimulatory CD40 ligand molecule will be useful as a new strategy of immunogene therapy against tumors.
590 11929124 OX40 (CD134), a membrane-bound member of the tumor-necrosis-factor-receptor superfamily, is expressed primarily on activated CD4+ T cells.
591 11929124 Recently, several groups have reduced clinical signs of autoimmunity in animal models by blocking the OX40-OX40-ligand interaction or depleting OX40+ T cells.
592 11929124 They include: (1) T cells isolated from a site of inflammation that express OX40 are T cells that have been stimulated recentlythrough the T-cell receptor in vivo; (2) OX40 is only expressed on T cells found at the site of inflammation, therefore, targeting this receptor does not interfere with the peripheral T-cell repertoire; and (3) the biological function of OX40 is limited primarily to effector CD4+ T cells, which are a major source of cytokines to induce and maintain ongoing immune responses.
593 11994434 Furthermore, MHC class II, B7-1, B7-2, and CD40 molecules were up-regulated.
594 11994440 IFN-alpha beta promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines.
595 11994440 Immunostimulatory sequence (ISS) DNA containing unmethylated CpG dinucleotides stimulate NK and APC to secrete proinflammatory cytokines, including IFN-alphabeta and -gamma, TNF-alpha, and IL-6 and -12, and to express costimulatory surface molecules such as CD40, B7-1, and B7-2.
596 11994440 This investigation examines the mechanisms by which ISS DNA primes CD8(+) and CD4(+) lymphocyte activities.
597 11994440 Coordinated regulation of B7 costimulation and TAP-dependent cross-presentation results in priming of Ag-specific CD8(+) CTL, whereas CD40, B7, and IL-12 costimulation is required for priming of CD4(+) Th cells by ISS-based vaccines.
598 11994440 IFN-alpha beta promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines.
599 11994440 Immunostimulatory sequence (ISS) DNA containing unmethylated CpG dinucleotides stimulate NK and APC to secrete proinflammatory cytokines, including IFN-alphabeta and -gamma, TNF-alpha, and IL-6 and -12, and to express costimulatory surface molecules such as CD40, B7-1, and B7-2.
600 11994440 This investigation examines the mechanisms by which ISS DNA primes CD8(+) and CD4(+) lymphocyte activities.
601 11994440 Coordinated regulation of B7 costimulation and TAP-dependent cross-presentation results in priming of Ag-specific CD8(+) CTL, whereas CD40, B7, and IL-12 costimulation is required for priming of CD4(+) Th cells by ISS-based vaccines.
602 12001037 Maximum plasma levels of interleukin (IL)-10 and soluble tumor necrosis factor receptor-II correlated with the degree of thrombocytopenia, independently of viremia levels.
603 12010968 PBMCs, cultivated with or without cytokines and exogenous CD40/CD40L signals, were stimulated with a crude parasite extract, recombinant vaccine candidates derived from conserved Ags (19-kDa C terminus of merozoite surface protein 1 [MSP1(19)], R23, and PfEB200), or recombinant Ags derived from the polymorphic Ags MSP1 block 2 and MSP2.
604 12010968 Optimal Ab production required addition of interleukin-2 (IL-2) and IL-10 for all antigenic preparations.
605 12036933 CD40L enhances the antigen presentation function of CD40-expressing B cells.
606 12036933 We have used a murine B-cell lymphoma model (A20) to study the in vivo antitumor effect of the administration of tumor cells transduced with a recombinant adenovirus encoding CD40L (AdvCD40L).
607 12036933 After infection with AdvCD40L, A20 tumor cells up-regulate several T-cell costimulatory molecules (CD80, CD86, ICAM-1, and LFA-3) and Fas expression.
608 12036933 In vivo depletion studies demonstrate that both CD4(+) and CD8(+) T cells mediate the antitumor immunity provided by AdvCD40L-transduced tumor cells.
609 12082460 We have constructed and tested five recombinant adenoviruses (Ads) that express a variety of immunomodulators, including CD40 ligand (CD40L), a potent costimulator of several components of the immune system.
610 12082460 Subsequently, using a therapeutic approach, we found that local, intratumoral coinjection of CD40L- and IL-2-expressing Ads was superior to any other agents tested and resulted in an at least 1.9-fold increase in mean survival time, in contrast to systemic application of recombinant CD40L or GM-CSF proteins, which had no significant effects.
611 12082460 When using vaccination as a therapeutic approach, the combinations of CD40L plus IL-2 or GM-CSF plus IL-2 from Ad gave rise to an extended (2.8-fold) increase in mean survival time.
612 12082460 A detailed analysis of immune cells present within regressing tumors indicated that mainly CD4(+) and CD8(+) T cells, and to a lesser extent dendritic cells, infiltrated the tumor mass, but not NK cells, macrophages, or granulocytes.
613 12082460 These results propose that a combination of CD40L plus IL-2 has an improved efficacy over the use of single agents when applied for direct in situ therapy or vaccination therapy.
614 12111121 Molecular requirements for CD8-mediated rejection of a MUC1-expressing pancreatic carcinoma: implications for tumor vaccines.
615 12111121 We confirmed that a CD8(+) effector cell was required to eliminate MUC1-expressing Panc02 tumors, and demonstrated that T cells expressing TCR-alpha/beta and co-stimulation through CD28 and CD40:CD40L interactions played critical roles during the initiation of the anti-Panc02.MUC1 immune response.
616 12111121 TCR-alpha/beta(+) cells were required to eliminate Panc02.MUC1 tumors, while TCR-gamma/delta(+) cells played a suppressive non-MUC1-specific role in anti-Panc02 tumor immunity.
617 12111121 Type 1 cytokine interferon-gamma (IFN-gamma), but not interleukin-12 (IL-12), was essential for eliminating MUC1-expressing tumors, while neither IL-4 nor IL-10 (type 2 cytokines) were required for tumor rejection.
618 12111121 In vitro studies demonstrated that IFN-gamma upregulated MHC class I, but not MHC class II, on Panc02.MUC1 tumor cells.
619 12111121 Surprisingly, both perforin and FasL played unique roles during the effector phase of immunity to Panc02.MUC1, while lymphotoxin-alpha, but not TNFR-1, was required for immunity against Panc02.MUC1 tumors.
620 12111122 We showed that bone marrow-derived DC pulsed with Id-CD40L upregulated the expression of CD40, CD80, CD86, and major histocompatibility complex (MHC) class II molecules with the increased production of interleukin-12 (IL-12).
621 12126895 Treating bone-marrow derived dendritic cells (BM-DCs) with CpG-enriched plasmids in vitro boosted their expressions of MHC class II molecules, the CD40 and CD86 activation markers.
622 12149218 Surprisingly, we found that for all maturation stimuli tested, the addition of prostaglandin E2 (PGE2) was required for effective migration of MoDCs toward the lymph node-derived chemokines CCL19 (EBI1 ligand chemokine/macrophage inflammatory protein--3beta) and CCL21 (secondary lymphoid tissue chemokine [SLC]/6Ckine).
623 12149218 Costimulation with PGE2 enhanced the expression of the CCL19/CCL21 receptor CCR7 on the cell surface of MoDCs when they were matured with soluble CD40 ligand or proinflammatory cytokines, but did not affect CCR7 expression of polyI:C-stimulated MoDCs.
624 12149218 The effects of PGE2 on MoDCs were mediated through increased cyclic adenosine monophosphate by 2 of the known PGE2 receptors, EP2 and EP4, which are expressed and down-regulated after PGE2 binding in these cells.
625 12176885 Efficient gene transfer of CD40 ligand into primary B-CLL cells using recombinant adeno-associated virus (rAAV) vectors.
626 12176885 Using an optimized adenovirus-free packaging system, recombinant adeno-associated virus (rAAV) vectors coding for the enhanced green fluorescent protein (AAV/EGFP) and CD40 ligand (AAV/CD40L) were packaged and highly purified resulting in genomic titers up to 3 x 10(11)/mL.
627 12176885 Cells obtained from 24 patients with B-CLL were infected with AAV/EGFP or AAV/CD40L at a multiplicity of infection (MOI) of 100 resulting in transgene expression in up to 97% of cells as detected by flow cytometry 48 hours after infection.
628 12176885 Transduction with AAV/CD40L resulted in up-regulation of the costimulatory molecule CD80 not only on infected CLL cells but also on noninfected bystander leukemia B cells, whereas this effect induced specific proliferation of HLA-matched allogeneic T cells.
629 12176885 Efficient gene transfer of CD40 ligand into primary B-CLL cells using recombinant adeno-associated virus (rAAV) vectors.
630 12176885 Using an optimized adenovirus-free packaging system, recombinant adeno-associated virus (rAAV) vectors coding for the enhanced green fluorescent protein (AAV/EGFP) and CD40 ligand (AAV/CD40L) were packaged and highly purified resulting in genomic titers up to 3 x 10(11)/mL.
631 12176885 Cells obtained from 24 patients with B-CLL were infected with AAV/EGFP or AAV/CD40L at a multiplicity of infection (MOI) of 100 resulting in transgene expression in up to 97% of cells as detected by flow cytometry 48 hours after infection.
632 12176885 Transduction with AAV/CD40L resulted in up-regulation of the costimulatory molecule CD80 not only on infected CLL cells but also on noninfected bystander leukemia B cells, whereas this effect induced specific proliferation of HLA-matched allogeneic T cells.
633 12189528 Enhanced HER-2/neu-specific antitumor immunity by cotransduction of mouse dendritic cells with two genes encoding HER-2/neu and alpha tumor necrosis factor.
634 12189528 The infected DCs (DC(HER-2/TNF-alpha)) displayed the expression of both HER-2/neu and TNF-alpha by flow cytometric and ELISA analysis.
635 12189528 We next investigated whether DC(HER-2/TNF-alpha) could induce stronger HER-2/neu-specific immune responses.
636 12189528 We found that DC(HER-2/TNF-alpha) displayed up-regulation of immunologically important CD40, CD86, and ICAM-I molecules compared with DC(HER-2), indicating that the former ones are more mature forms of DCs.
637 12189528 Vaccination of DC(HER-2/TNF-alpha) induced stronger allogeneic T-cell proliferation and 36% enhanced HER-2/neu-specific T-cell responses in vitro than DC(HER-2) cells.
638 12191571 DC(RMAT) displayed an up-regulated expression of immune molecules (Ia(d), CD40, CD54, CD80 and CD86) and certain cytokines/chemokines, and enhanced ability of allogeneic T cell stimulation when compared to DC(IMAT).
639 12200675 Gene transfer of CD154 and IL12 cDNA induces an anti-leukemic immunity in a murine model of acute leukemia.
640 12200675 CD154 triggers CD40 on antigen-presenting cells, thus inducing antigen presentation to the immune system and production of IL12.
641 12200675 As IL12 and CD154 share several pathways mediating immune response, we investigated in an aggressive murine model of acute leukemia the relative antileukemic efficiency of IL12, CD154 and IL12 + CD154 gene transfer.
642 12200675 Live leukemic cells transduced by IL12, CD154, and IL12 + CD154 showed reduced leukemogenicity but CD154 protective effect was reduced when 10(6) leukemic cells were injected.
643 12200675 NK cytotoxicity was enhanced in mice vaccinated with leukemic cells transduced by IL12, CD154, and CD154 + IL12.
644 12200675 IL12 transduced cells induced IFN-gamma mRNA in CD4(+) and CD8(+) T cells isolated from the spleen of vaccinated animals, however, in vivo depletion experiments showed that IL12 vaccine effect was CD4(+) but not CD8(+) T cell dependent.
645 12200675 We conclude that IL12 gene is a more potent candidate than CD154 for gene therapy of acute leukemia.
646 12207346 The transition from monocyte to DC is characterized by the up-regulation of CD83, CD86, CD80, CD40 and the down-regulation of CD14.
647 12357348 In particular, ex vivo culture of ALL cells with CD40 ligand, incubation of AML cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 (GM-CSF/IL-4) and lentiviral transduction of ALL and AML cells for expression of immunomodulators (CD80 and GM-CSF) are current approaches under investigation for the development of autologous acute leukemia cell vaccines.
648 12385027 In vivo receptor-mediated delivery of a recombinant invasive bacterial toxoid to CD11c + CD8 alpha -CD11bhigh dendritic cells.
649 12385027 Here we show that CyaA, the adenylate cyclase toxin of Bordetella pertussis, an invasive bacterial toxin that binds cells through CD11b/CD18 can be exploited for the targeted delivery of an exogenous peptide to the CD8 alpha -CD11bhigh subset in vivo.
650 12385027 Antigen (Ag) genetically inserted in the N-terminal domain of mutant CyaA devoid of catalytic activity, are targeted to CD8 alpha -CD11bhigh DC by the CD11b/CD18-dependent binding of CyaA to the cell surface.
651 12385027 As a result, CTL are primed after a single injection, bypassing requirement for adjuvant, CD4+ T cell help and CD40 signaling.
652 12385027 Beside the interest of the CyaA vector for vaccine development, these results show that Ag presentation focused on CD8 alpha -CD11bhigh DC in vivo is sufficient for eliciting a vigorous CTL response and that CD11b/CD18 could be a suitable surface molecule for targeting Ag to DC.
653 12391201 CD28, TNF receptor, and IL-12 are critical for CD4-independent cross-priming of therapeutic antitumor CD8+ T cells.
654 12391201 Previously, we have shown that priming of therapeutic CD8(+) T cells in tumor vaccine-draining lymph nodes of mice vaccinated with GM-CSF secreting B16BL6 melanoma cells occurs independent of CD4 T cell help.
655 12391201 In this study, we examined the contribution of the major costimulatory molecules, CD40 ligand (CD40L), CD80, and CD86, in the priming of CD8(+) T cells.
656 12391201 Priming of therapeutic CD8(+) T cells by a GM-CSF-transduced tumor vaccine did not require CD40 and CD40L interactions, as therapeutic T cells could be generated from mice injected with anti-CD40L Ab and from CD40L knockout mice.
657 12391201 However, costimulation via either CD80 or CD86 was required, as therapeutic T cells could be generated from mice injected with either anti-CD80 or anti-CD86 Ab alone, but administration of both Abs completely inhibited the priming of therapeutic T cells.
658 12391201 Blocking experiments also identified that priming of therapeutic T cells in MHC class II-deficient mice required TNFR and IL-12 signaling, but signaling through CD40, lymphotoxin-betaR, or receptor activator of NF-kappaB was not essential.
659 12391201 Thus, cross-priming of therapeutic CD8(+) T cells by a tumor vaccine transduced with GM-CSF requires TNFR, IL-12, and CD28 signaling.
660 12391201 CD28, TNF receptor, and IL-12 are critical for CD4-independent cross-priming of therapeutic antitumor CD8+ T cells.
661 12391201 Previously, we have shown that priming of therapeutic CD8(+) T cells in tumor vaccine-draining lymph nodes of mice vaccinated with GM-CSF secreting B16BL6 melanoma cells occurs independent of CD4 T cell help.
662 12391201 In this study, we examined the contribution of the major costimulatory molecules, CD40 ligand (CD40L), CD80, and CD86, in the priming of CD8(+) T cells.
663 12391201 Priming of therapeutic CD8(+) T cells by a GM-CSF-transduced tumor vaccine did not require CD40 and CD40L interactions, as therapeutic T cells could be generated from mice injected with anti-CD40L Ab and from CD40L knockout mice.
664 12391201 However, costimulation via either CD80 or CD86 was required, as therapeutic T cells could be generated from mice injected with either anti-CD80 or anti-CD86 Ab alone, but administration of both Abs completely inhibited the priming of therapeutic T cells.
665 12391201 Blocking experiments also identified that priming of therapeutic T cells in MHC class II-deficient mice required TNFR and IL-12 signaling, but signaling through CD40, lymphotoxin-betaR, or receptor activator of NF-kappaB was not essential.
666 12391201 Thus, cross-priming of therapeutic CD8(+) T cells by a tumor vaccine transduced with GM-CSF requires TNFR, IL-12, and CD28 signaling.
667 12391201 CD28, TNF receptor, and IL-12 are critical for CD4-independent cross-priming of therapeutic antitumor CD8+ T cells.
668 12391201 Previously, we have shown that priming of therapeutic CD8(+) T cells in tumor vaccine-draining lymph nodes of mice vaccinated with GM-CSF secreting B16BL6 melanoma cells occurs independent of CD4 T cell help.
669 12391201 In this study, we examined the contribution of the major costimulatory molecules, CD40 ligand (CD40L), CD80, and CD86, in the priming of CD8(+) T cells.
670 12391201 Priming of therapeutic CD8(+) T cells by a GM-CSF-transduced tumor vaccine did not require CD40 and CD40L interactions, as therapeutic T cells could be generated from mice injected with anti-CD40L Ab and from CD40L knockout mice.
671 12391201 However, costimulation via either CD80 or CD86 was required, as therapeutic T cells could be generated from mice injected with either anti-CD80 or anti-CD86 Ab alone, but administration of both Abs completely inhibited the priming of therapeutic T cells.
672 12391201 Blocking experiments also identified that priming of therapeutic T cells in MHC class II-deficient mice required TNFR and IL-12 signaling, but signaling through CD40, lymphotoxin-betaR, or receptor activator of NF-kappaB was not essential.
673 12391201 Thus, cross-priming of therapeutic CD8(+) T cells by a tumor vaccine transduced with GM-CSF requires TNFR, IL-12, and CD28 signaling.
674 12393401 Using confocal microscopy we have confirmed our previous observation that heat-stressed apoptotic 12B1-D1 leukemia cells (BCR-ABL(+)) express HSP60 and HSP72 on their surface.
675 12393401 However, when stressed apoptotic 12B1-D1 cells were coincubated with immature dendritic cells for 24 hours, this resulted in greater up-regulation of costimulatory molecules (CD40, CD80, and CD86) on the surface of dendritic cells.
676 12427285 Of the TNFSF molecules, CD40 ligand (CD40L, also called CD154 or TNFSF5) is the most crucial molecule for activating antigen-presenting cells (APCs) and thereby initiating the immune response.
677 12427285 Evidence has accrued indicating that HIV infection either selectively depletes those CD4(+) T cells that express CD40L in response to antigen or down-regulates CD40L expression by these cells.
678 12427285 CD40L contributes to the antiviral mechanisms of the host by inducing anti-HIV beta-chemokines and activating CD8(+) T cells.
679 12430862 Recent studies indicate that the stealth-like phenotype of leukemia cells can be reversed through transfer of genes encoding recombinant membrane-stabilized proteins of the tumor necrosis factor (TNF) imily, such as the one encoding CD154, the ligand for CD40.
680 12439347 In general, DC phenotype was CD14(low), CD86(high), CD40(high), CD80(low), and CD83(low).
681 12445291 In natural immune responses CD4+ T helper (Th) cells, reactive with peptide antigens presented by major histocompatibility complex (MHC) class II molecules on dendritic cells (DC), can drive the maturation of DC that is required for induction of CD8+ cytolytic T-lymphocyte (CTL) immunity.
682 12445291 Proper induction, expansion and maintenance of CTL responses are achieved through delicate interactions between CD4+ T cells, DC and CD8+ T cells involving several ligand-receptor pairs.
683 12445291 Th cells to a large extent operate through up-regulation of CD40L, which then interacts with CD40 on DC to cause DC maturation.
684 12445291 Subsequent CTL induction by activated DC requires CD80/CD86 on the DC to interact with the CD28 costimulatory receptor on CD8+ T cells.
685 12445291 Alternative molecular triggers of DC activation that can support induction of powerful CTL responses include agonistic anti-CD40 antibody or ligands of Toll-like receptors (TLR) such as LPS (TLR4 ligand) or oligodeoxynucleotides containing CpG-motifs (TLR9 ligand).
686 12460195 Furthermore, after exposure to BCG-infected necrotic macrophages, DCs underwent phenotypic changes, including the up-regulation of maturation specific markers (major histocompatibility complex class II, CD40, CD80, and CD86) and the capacity to stimulate antigen-specific CD4+ T cells with higher efficiency than when they were directly infected with a similar number of bacteria.
687 12460195 Antigen presentation following phagocytosis of BCG-infected necrotic macrophages was demonstrated by their ability to stimulate in vitro proliferation and interferon-gamma production of antigen-specific CD4+ T cells.
688 12477423 We compared the standard maturation stimulus, autologous monocyte-conditioned medium (MCM), with a synthetic double stranded RNA (poly I:C), soluble CD40 ligand trimer, and a defined cocktail of cytokines (TNF-alpha, IL-1 beta, IL-6) and PGE(2) to promote mature phenotype and function in human monocyte-derived DCs.
689 12487060 Another study examined this issue by studying prostatic acid phosphatase (PAP) protein-loaded mature DCs injected intravenously, intradermally, and intralymphatically in prostate cancer patients [45].
690 12487060 Regardless of route of administration, T cell responses were induced as measured by proliferation when PBMCs in vitro were stimulated with the PAP protein.
691 12487060 A number of studies have demonstrated that maturation signals such as inflammatory cytokines and CD40 ligation lead to down-regulation of antigen processing and up-regulation of the chemokine receptor CCR7, which leads to homing to lymph nodes [46] as well as the MHC molecules, costimulatory molecules, and maturation markers [8,47,48].
692 12487060 One study using CEA peptides and CEA RNA found that optimal T cell presentation occurs when peptides are loaded after maturation with CD40 ligand and when RNA is transfected before maturation with CD40 ligand [53].
693 12487060 Many use DTH responses, but these may measure CD4 T cells instead of CD8 T cells.
694 12487060 Others have monitored the decrease in serum tumor markers such as PSA or CEA.
695 12487060 Another study examined this issue by studying prostatic acid phosphatase (PAP) protein-loaded mature DCs injected intravenously, intradermally, and intralymphatically in prostate cancer patients [45].
696 12487060 Regardless of route of administration, T cell responses were induced as measured by proliferation when PBMCs in vitro were stimulated with the PAP protein.
697 12487060 A number of studies have demonstrated that maturation signals such as inflammatory cytokines and CD40 ligation lead to down-regulation of antigen processing and up-regulation of the chemokine receptor CCR7, which leads to homing to lymph nodes [46] as well as the MHC molecules, costimulatory molecules, and maturation markers [8,47,48].
698 12487060 One study using CEA peptides and CEA RNA found that optimal T cell presentation occurs when peptides are loaded after maturation with CD40 ligand and when RNA is transfected before maturation with CD40 ligand [53].
699 12487060 Many use DTH responses, but these may measure CD4 T cells instead of CD8 T cells.
700 12487060 Others have monitored the decrease in serum tumor markers such as PSA or CEA.
701 12489023 CD40, a member of the tumor necrosis factor receptor (TNF-R) family, is a surface receptor best known for its capacity to initiate multifaceted activation signals in normal B cells and dendritic cells (DCs).
702 12489023 CD40-related treatment approaches have been considered for the experimental therapy of human leukemias, lymphomas, and multiple myeloma, based on findings that CD40 binding by its natural ligand (CD40L), CD154, led to growth modulation of malignant B cells.
703 12489023 CD40, a member of the tumor necrosis factor receptor (TNF-R) family, is a surface receptor best known for its capacity to initiate multifaceted activation signals in normal B cells and dendritic cells (DCs).
704 12489023 CD40-related treatment approaches have been considered for the experimental therapy of human leukemias, lymphomas, and multiple myeloma, based on findings that CD40 binding by its natural ligand (CD40L), CD154, led to growth modulation of malignant B cells.
705 12496388 OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response.
706 12496388 Efficient T cell priming by GM-CSF and CD40 ligand double-transduced C26 murine colon carcinoma is not sufficient to cure metastases in a therapeutic setting.
707 12496388 To determine whether a cellular vaccine that interacts directly with both APC and T cells in vivo might be superior, we generated C26 carcinoma cells transduced with the T cell costimulatory molecule OX40 ligand (OX40L) either alone (C26/OX40L) or together with GM-CSF (C26/GM/OX40L), which is known to activate APC.
708 12496388 Tumor rejection required granulocytes, CD4+, CD8+ T cells, and APC-mediated CD40-CD40 ligand cosignaling, but not IFN-gamma or IL-12 as shown using subset-depleted and knockout (KO) mice.
709 12496388 Indeed, CD4+ T cell-depleted mice failed to mount any CTL activity against the C26 tumor, while treatment with agonistic mAb to CD40, which acts on APC, bypassed the requirement for CD4+ T cells and restored CTL activation.
710 12496388 OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response.
711 12496388 Efficient T cell priming by GM-CSF and CD40 ligand double-transduced C26 murine colon carcinoma is not sufficient to cure metastases in a therapeutic setting.
712 12496388 To determine whether a cellular vaccine that interacts directly with both APC and T cells in vivo might be superior, we generated C26 carcinoma cells transduced with the T cell costimulatory molecule OX40 ligand (OX40L) either alone (C26/OX40L) or together with GM-CSF (C26/GM/OX40L), which is known to activate APC.
713 12496388 Tumor rejection required granulocytes, CD4+, CD8+ T cells, and APC-mediated CD40-CD40 ligand cosignaling, but not IFN-gamma or IL-12 as shown using subset-depleted and knockout (KO) mice.
714 12496388 Indeed, CD4+ T cell-depleted mice failed to mount any CTL activity against the C26 tumor, while treatment with agonistic mAb to CD40, which acts on APC, bypassed the requirement for CD4+ T cells and restored CTL activation.
715 12513792 The phenotype of DC was detected by FCM with CD1a, CD40, CD80, CD86, HLA-A, B, C and HLA-DR monoclonal antibodies.
716 12513792 The level of IL-12 and IFN-gamma in supernatant of DC culture was measured by ELISA.
717 12513792 A high expression of phenotypes was found in HL-60-DC and THP-1-DC stimulated by GM-CSF + IL-4 + TNF-gamma and K562-DC with GM-CSF + IL-4 + IL-12.
718 12517965 The objective of this study was to test the ability of bovine CD154 to target a plasmid-encoded Ag to CD40-expressing APCs.
719 12517965 To achieve this, a plasmid coding for bovine CD154 fused to a truncated secreted form of bovine herpesvirus 1 glycoprotein D (tgD), pSLIAtgD-CD154, was constructed.
720 12517965 The chimeric tgD-CD154 was expressed in vitro in COS-7 cells and reacted with both glycoprotein D- and CD154-specific Abs.
721 12536236 The ability of acute myeloid leukaemia (AML) cells to acquire dendritic cell (DC)-like characteristics in vitro with a rapid culture method based either on the phorbol ester PMA or calcium ionophores has been studied in comparison to conventional AML-DC cultures with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha), interleukin-3 (IL-3), SCF, FLT3-L and IL-4.
722 12536236 The most mature APC were generated by calcium ionophore A23187 plus IL-4, as evidenced by the higher expression of CD40, CD80, CD86 and HLA-DR.
723 12540559 We here report that BALB/c interleukin-4 knockout (IL-4(-/-)) mice are weakly overcolonized compared to the wt strain but that the IL-12(-/-) knockout results in a strong overcolonization (500%).
724 12540559 The IL-4(-/-) mutation caused a 50% reduction and the IL-12(-/-) knockout caused a 95% reduction compared to the wt colonization rate.
725 12540559 For C57BL/6J mice we further analyzed the IL-18(-/-) and Toll-like receptor 2 knockout mutations, which showed reductions to 66 and 57%, respectively, whereas mice with the IL-10(-/-) phenotype were hardly infected at all (5%).
726 12540559 In contrast, the tumor necrosis factor receptor knockout (p55(-/-) and p55/75(-/-)) mice showed an overcolonization compared to the C57BL/6J wt strain.
727 12540559 With exception of the low-level infected C57BL/6J IL-10(-/-) and IL-12(-/-) knockout mice, all knockout mutants were accessible to a prophylactic vaccination and their vaccination behavior was comparable to that of the wt strains.
728 12552458 This study shows that human blood monocyte-derived dendritic cells loaded with liposome-complexed HIV-1 proteins and matured with CD40 ligand can prime CD8(+) T cells to HIV-1 in vitro.
729 12562324 APC from CD40 knockout mice were as effective as wild-type APC for the induction of non-specific and GXM-specific responses.
730 12562324 Blocking activity of B7-1 and B7-2 by treatment of immunized mice with monoclonal antibodies specific for these molecules just before and for 6 days following GXM-APC immunization decreased the splenic interferon-gamma response of mice subsequently infected with NU-2, but only in mice that were treated with both antibodies.
731 12562326 Our data shows that transfection of DCs with recombinant adenovirus AdV-TNF-alpha resulted in greater maturation of the DCs than occurred with control DCs cultured in exogenous TNF-alpha, as determined by up-regulated expression of pro-inflammatory cytokines (e.g. interleukins 1beta and 18), chemokines [e.g. interferon-gamma-inducible protein-10 and macrophage inflammatory protein-1beta (MIP-1beta)], the CC chemokine receptor CCR7, and immunologically important cell surface molecules (CD40, CD86 and intercellular adhesion molecule-1).
732 12562326 Our data also demonstrate that vaccination of mice with Mut1 peptide-pulsed, AdV-TNF-alpha-transfected DCs stimulated more efficient in vitro Mut1-specific CD8+ cytotoxic T-cell responses and solid tumour immunity in vivo, when compared to the in vitro TNF-alpha-cultivated DCs.
733 12576309 We found that DCs incubated with 12B1-derived CRCL had higher expression of CD40 and major histocompatibility complex class II (MHC-II) on their cell surface, produced more interleukin-12 (IL-12), and had superior immunostimulatory capacity in a mixed leukocyte reaction (MLR) when compared with DCs exposed to unfractionated tumor lysate or purified heat-shock protein 70 (HSP70).
734 12576309 The protective immunity generated was tumor specific, long lasting, and both CD4+ and CD8+ T-cell dependent.
735 12618487 In a previous study we showed that immunization with dendritic cells (DC) pulsed with idiotype (Id) fused with CD40 ligand (CD40L) could break the tolerance to Id which is expressed on B lymphoma cells and restored the responsiveness of T(h) cells, and, subsequently, induced IgG antibody response.
736 12618487 On examining the mechanism for this isotype change, we found that IFN-gamma production by CD4(+) T cells is not the only determining factor for achieving a successful therapy.
737 12618487 The deciding factor appears to be the abrogation of IL-4 production that was achieved by combing with IL-12 gene therapy.
738 12626578 In this report we show that the dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1 (DC-CK1), which is produced in humans and acts on naive lymphocytes, can enhance Ag-specific CD8(+) T cell responses when coadministered with either irradiated Plasmodium yoelii sporozoites or a recombinant adenovirus expressing the P. yoelii circumsporozoite protein in mice.
739 12626578 DC-CK1 appears to act preferentially on naive mouse lymphocytes, and its adjuvant effect requires IL-12, but not IFN-gamma or CD40.
740 12639819 OM-197 upregulated the expression of HLA-DR, CD80, CD86, CD83, CD40 and CD54 at the surface of myeloid DC naturally present in blood as well as of DC generated in vitro from monocytes using IL-4 and GM-CSF.
741 12639819 OM-197 also induced the release of IL-12 and TNF-alpha from DC.
742 12639819 Finally, DC incubated with OM-197 after pulsing with hepatitis B surface antigen (HBs Ag) induced in vitro expansion of IFN-gamma-secreting HBs Ag-specific CD4(+) T lymphocytes from naive individuals.
743 12672905 We showed that BCG could promote cord blood monocyte-derived DC maturation by up-regulation of CD80, CD83, CD86, CD40, and MHC class II molecules and down-regulation of mannose receptor.
744 12672905 BCG was able to induce similar levels of tumor necrosis factor-alpha and IL-10 but no bioactive IL-12p70 production from cord blood DCs as from adult blood DCs.
745 12672905 Both non-BCG-treated and BCG-treated cord blood DCs efficiently induced a high level of IL-10, medium level of interferon-gamma, but little IL-4 production by cord blood naïve CD4+ T cells.
746 12672905 Heat shock protein 65, a key component of BCG, had no effect on cord blood DC maturation in terms of CD86, MHC class II, and mannose receptor up-regulation.
747 12682236 It is widely believed that generation of mature dendritic cells (DCs) with full T cell stimulatory capacity from human monocytes in vitro requires 5-7 days of differentiation with GM-CSF and IL-4, followed by 2-3 days of activation.
748 12682236 Monocytes acquire immature DC characteristics by day 2 of culture with GM-CSF and IL-4; they down-regulate CD14, increase dextran uptake, and respond to the inflammatory chemokine macrophage inflammatory protein-1alpha.
749 12682236 To accelerate DC development and maturation, monocytes were incubated for 24 h with GM-CSF and IL-4, followed by activation with proinflammatory mediators for another 24 h (FastDC).
750 12682236 FastDC expressed mature DC surface markers as well as chemokine receptor 7 and secreted IL-12 (p70) upon CD40 ligation in the presence of IFN-gamma.
751 12682236 The increase in intracellular calcium in response to 6Ckine showed that chemokine receptor 7 expression was functional.
752 12684428 TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients.
753 12695492 The two major subsets of invariant NKT cells, CD4+ and double negative (CD4-CD8-), express comparable levels of CD40 ligand and cytokines, but differ in helper functions.
754 12699364 Cytokine and chemokine combinations can potentially help target antigen to the appropriate antigen presenting cell and initiate maturation of these presenting cells, attract cells expressing different chemokine receptors, steer cellular immune responses toward Th1 and CD8 CTL, and enhance systemic and mucosal IgG and secretory IgA antibodies and determine their isotype balance.
755 12699364 For example, GM-CSF has been shown to be synergistic with IL-12 or CD40 ligand for induction of CTL and for antiviral protection, and the triple combination of GM-CSF, IL-12, and TNF alpha appears to induce the most effective protection in some mouse models.
756 12718765 Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to B-chronic lymphocytic leukemia cells.
757 12718765 CD40 ligand (CD40L) is a good candidate molecule for the immunotherapy of B cell malignancies including B-chronic lymphocytic leukemia (B-CLL), because it may increase the capacity of the malignant cells to present tumor antigens.
758 12718765 The malignant cells expressed high levels of surface hCD40L, B7-1, B7-2, and ICAM-1 after coculture.
759 12718765 Upregulation of B7-1 and B7-2 was cycloheximide inhibitable and was a consequence of CD40 activation.
760 12718765 However, inhibition of protein synthesis had no effect on the ability of B-CLL cells to acquire surface expression of hCD40L. hCD40L surface expression required cell-to-cell contact, but was independent of CD40 engagement. hCD40L transfer was not mediated by membrane fusion.
761 12718765 The transferred hCD40L was functionally intact and B-CLL cells expressing this molecule induced increased interferon-gamma production from autologous peripheral blood T lymphocytes.
762 12718765 Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to B-chronic lymphocytic leukemia cells.
763 12718765 CD40 ligand (CD40L) is a good candidate molecule for the immunotherapy of B cell malignancies including B-chronic lymphocytic leukemia (B-CLL), because it may increase the capacity of the malignant cells to present tumor antigens.
764 12718765 The malignant cells expressed high levels of surface hCD40L, B7-1, B7-2, and ICAM-1 after coculture.
765 12718765 Upregulation of B7-1 and B7-2 was cycloheximide inhibitable and was a consequence of CD40 activation.
766 12718765 However, inhibition of protein synthesis had no effect on the ability of B-CLL cells to acquire surface expression of hCD40L. hCD40L surface expression required cell-to-cell contact, but was independent of CD40 engagement. hCD40L transfer was not mediated by membrane fusion.
767 12718765 The transferred hCD40L was functionally intact and B-CLL cells expressing this molecule induced increased interferon-gamma production from autologous peripheral blood T lymphocytes.
768 12718765 Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to B-chronic lymphocytic leukemia cells.
769 12718765 CD40 ligand (CD40L) is a good candidate molecule for the immunotherapy of B cell malignancies including B-chronic lymphocytic leukemia (B-CLL), because it may increase the capacity of the malignant cells to present tumor antigens.
770 12718765 The malignant cells expressed high levels of surface hCD40L, B7-1, B7-2, and ICAM-1 after coculture.
771 12718765 Upregulation of B7-1 and B7-2 was cycloheximide inhibitable and was a consequence of CD40 activation.
772 12718765 However, inhibition of protein synthesis had no effect on the ability of B-CLL cells to acquire surface expression of hCD40L. hCD40L surface expression required cell-to-cell contact, but was independent of CD40 engagement. hCD40L transfer was not mediated by membrane fusion.
773 12718765 The transferred hCD40L was functionally intact and B-CLL cells expressing this molecule induced increased interferon-gamma production from autologous peripheral blood T lymphocytes.
774 12718765 Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to B-chronic lymphocytic leukemia cells.
775 12718765 CD40 ligand (CD40L) is a good candidate molecule for the immunotherapy of B cell malignancies including B-chronic lymphocytic leukemia (B-CLL), because it may increase the capacity of the malignant cells to present tumor antigens.
776 12718765 The malignant cells expressed high levels of surface hCD40L, B7-1, B7-2, and ICAM-1 after coculture.
777 12718765 Upregulation of B7-1 and B7-2 was cycloheximide inhibitable and was a consequence of CD40 activation.
778 12718765 However, inhibition of protein synthesis had no effect on the ability of B-CLL cells to acquire surface expression of hCD40L. hCD40L surface expression required cell-to-cell contact, but was independent of CD40 engagement. hCD40L transfer was not mediated by membrane fusion.
779 12718765 The transferred hCD40L was functionally intact and B-CLL cells expressing this molecule induced increased interferon-gamma production from autologous peripheral blood T lymphocytes.
780 12744857 Here, we report on the production of a bacterially expressed bispecific conjugate, consisting of a fusion of recombinant single-chain (sc) mAb Fv fragments, which bind and neutralize the Ad fiber knob (through the S11 mAb scFv) and retarget Ad to CD40 on the DC surface (through the G28-5 mAb scFv).
781 12798640 CD40 ligand (CD154) improves the durability of respiratory syncytial virus DNA vaccination in BALB/c mice.
782 12798640 In this study, we examine CD40 ligand (CD40L) as an immune modulator to enhance the durability of DNA vaccines encoding RSV F and/or G glycoproteins in BALB/c mice.
783 12798640 CD40 ligand (CD154) improves the durability of respiratory syncytial virus DNA vaccination in BALB/c mice.
784 12798640 In this study, we examine CD40 ligand (CD40L) as an immune modulator to enhance the durability of DNA vaccines encoding RSV F and/or G glycoproteins in BALB/c mice.
785 12807483 Resting bone marrow DC pulsed with ovalbumin ISCOMS efficiently prime resting CD8+ T cells through a mechanism that is transporter associated with antigen processing (TAP) dependent, but independent of CD40 ligation and CD4+ T-cell help.
786 12807483 Lipopolysaccharide-induced maturation of DC markedly enhances their ability to prime CD8+ T cells through a mechanism which is also independent of CD4+ T-cell help, but is dependent on CD40 ligation.
787 12807483 Resting bone marrow DC pulsed with ovalbumin ISCOMS efficiently prime resting CD8+ T cells through a mechanism that is transporter associated with antigen processing (TAP) dependent, but independent of CD40 ligation and CD4+ T-cell help.
788 12807483 Lipopolysaccharide-induced maturation of DC markedly enhances their ability to prime CD8+ T cells through a mechanism which is also independent of CD4+ T-cell help, but is dependent on CD40 ligation.
789 12832444 Three DC functions that may be critical for immunization potential are expression of CD80/86, cytokine production following CD40 engagement, and migration to chemokine receptor 7-binding chemokines.
790 12832444 Although high expression of CD80/86 and migration to 6Ckine + macrophage-inflammatory protein-3beta were properties of mature DC, cytokine production following CD40 ligation was superior by immature DC.
791 12832444 Three DC functions that may be critical for immunization potential are expression of CD80/86, cytokine production following CD40 engagement, and migration to chemokine receptor 7-binding chemokines.
792 12832444 Although high expression of CD80/86 and migration to 6Ckine + macrophage-inflammatory protein-3beta were properties of mature DC, cytokine production following CD40 ligation was superior by immature DC.
793 12839929 Efficient VLP cross-presentation by Langerhans cells with costimulation can be achieved by addition of CD40 ligand.
794 12850495 Both interleukin-4 and CD40 ligand are important for optimal dendritic cell differentiation and maturation.
795 12850495 Granulocyte-monocyte colony-stimulating factor, interleukin-4, and CD40 ligand in combination are capable of yielding dendritic cells from at least some cases of acute lymphocytic leukemia.
796 12850495 Both interleukin-4 and CD40 ligand are important for optimal dendritic cell differentiation and maturation.
797 12850495 Granulocyte-monocyte colony-stimulating factor, interleukin-4, and CD40 ligand in combination are capable of yielding dendritic cells from at least some cases of acute lymphocytic leukemia.
798 12862419 Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia.
799 12862419 DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts.
800 12862419 The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts.
801 12862419 Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs.
802 12862419 Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs.
803 12862419 Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia.
804 12862419 DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts.
805 12862419 The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts.
806 12862419 Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs.
807 12862419 Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs.
808 12862419 Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia.
809 12862419 DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts.
810 12862419 The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts.
811 12862419 Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs.
812 12862419 Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs.
813 12862419 Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia.
814 12862419 DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts.
815 12862419 The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts.
816 12862419 Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs.
817 12862419 Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs.
818 12874017 Activation of CD40 by CD154 induces antigen-presenting cells (APC) to express immune costimulatory molecules, thereby enhancing their APC activity.
819 12902478 We now report that direct activation of protein kinase C (PKC) by the phorbol ester PMA in the BCR-ABL(+) CML cell line K562 and primary CML blasts induced nonterminal differentiation into cells with typical DC morphology (cytoplasmic dendrites), characteristic surface markers (MHC class I, MHC class II, CD86, CD40), chemokine and transcription factor expression, and ability to stimulate T cell proliferation (equivalent to normal monocyte-derived DC).
820 12928384 Regulation of the class II MHC pathway in primary human monocytes by granulocyte-macrophage colony-stimulating factor.
821 12928384 GM-CSF also increases expression of the costimulatory molecules CD86 and CD40, but not the differentiation marker CD1a or CD16.
822 12928384 Expression of class II transactivator (CIITA) types I and III, but not IV, transcripts increases in response to GM-CSF.
823 12928384 Furthermore, GM-CSF increases the amount of CIITA associated with the DR promoter.
824 12928384 Thus, our data argue that the proinflammatory role of GM-CSF is mediated in part through increased expression of key molecules involved in the class II MHC pathway via induction of CIITA.
825 12933866 Maturation markers (i.e., CD80, CD86, major histocompatibility complex class II, and CD40) showed enhanced expression on DC incubated with targeted PorA liposomes relative to those incubated with nontargeted PorA liposomes.
826 12941150 CD40/CD154 interaction is essential for both humoral and cellular immune response.
827 12941150 To that aim, we measured the levels of the soluble form of CD40 (sCD40), which is known to interfere with CD40/CD154 interaction, in 43 chronic renal failure patients, 162 hemodialysed patients, and 83 healthy donors.
828 12941150 CD40/CD154 interaction is essential for both humoral and cellular immune response.
829 12941150 To that aim, we measured the levels of the soluble form of CD40 (sCD40), which is known to interfere with CD40/CD154 interaction, in 43 chronic renal failure patients, 162 hemodialysed patients, and 83 healthy donors.
830 12947333 CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy.
831 12969546 CD1a and CD1c cell sorting yields a homogeneous population of immature human Langerhans cells.
832 12969546 CD1c selection yielded a homogeneous population of pure and viable HLA-DR(+)/CD1a(+) DCs, with the ultrastructural features, surface antigen expression and cytokine profile, characteristic of epidermis-resident immature LCs.
833 12969546 Characterizing the cells in more detail, we could demonstrate for the first time that normal human LCs express CXCR4, CD40 ligand (CD40L), and Fas and Fas ligand (FasL).
834 12969546 LPS and IFN-omega stimulated the expression of the inflammatory cytokines TNF-alpha and IL-1beta, and there was secretion of IL-12p70 after CD40 ligation.
835 12969546 CD1a and CD1c cell sorting yields a homogeneous population of immature human Langerhans cells.
836 12969546 CD1c selection yielded a homogeneous population of pure and viable HLA-DR(+)/CD1a(+) DCs, with the ultrastructural features, surface antigen expression and cytokine profile, characteristic of epidermis-resident immature LCs.
837 12969546 Characterizing the cells in more detail, we could demonstrate for the first time that normal human LCs express CXCR4, CD40 ligand (CD40L), and Fas and Fas ligand (FasL).
838 12969546 LPS and IFN-omega stimulated the expression of the inflammatory cytokines TNF-alpha and IL-1beta, and there was secretion of IL-12p70 after CD40 ligation.
839 13680192 Combination of monocyte-derived dendritic cells and activated T cells which express CD40 ligand: a new approach to cancer immunotherapy.
840 13680192 To develop the basis for a new DC-based cancer vaccine, we investigated cell-to-cell interactions between human monocyte-derived DCs and autologous T cells that are activated to express the CD40 ligand (CD40L).
841 13680192 Peripheral blood monocytes were cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) to induce differentiation of DCs.
842 13680192 Coculture of these DCs and ATs induced significant production of interleukin 12 (IL-12) and also enhanced the production of interferon gamma (IFN-gamma).
843 13680192 Furthermore, coculture of DCs and ATs induced DCs to upregulate CD83 expression and stimulated migration of DCs toward the macrophage inflammatory protein 3-beta (MIP-3beta).
844 13680192 Combination of monocyte-derived dendritic cells and activated T cells which express CD40 ligand: a new approach to cancer immunotherapy.
845 13680192 To develop the basis for a new DC-based cancer vaccine, we investigated cell-to-cell interactions between human monocyte-derived DCs and autologous T cells that are activated to express the CD40 ligand (CD40L).
846 13680192 Peripheral blood monocytes were cultured in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) to induce differentiation of DCs.
847 13680192 Coculture of these DCs and ATs induced significant production of interleukin 12 (IL-12) and also enhanced the production of interferon gamma (IFN-gamma).
848 13680192 Furthermore, coculture of DCs and ATs induced DCs to upregulate CD83 expression and stimulated migration of DCs toward the macrophage inflammatory protein 3-beta (MIP-3beta).
849 14500478 Parent OM selectively up-regulated Toll-like receptor 4 (TLR4) mRNA expression and induced mo-DC maturation, as reflected by increased production of chemokines, proinflammatory cytokines, and CD83, CD80, CD86, CD40, and major histocompatibility complex (MHC) class II molecules.
850 14500478 In contrast, LPS-deficient OM selectively up-regulated TLR2 mRNA expression and induced moderate increases in both cytokine production and expression of CD86 and MHC class II molecules.
851 14502286 Activation of cross-priming by IFN-alpha/beta was independent of CD4+ T cell help or interaction of CD40 and CD40 ligand, and involved direct stimulation of dendritic cells.
852 14504106 We first observed that neonatal pDCs displayed decreased up-regulation of CD80, CD83, CD86, and CD40, whereas HLA-DR and CD54 up-regulation did not differ significantly between adults and neonates.
853 14530334 Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B (RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen.
854 14530334 In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses.
855 14530334 We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs.
856 14530334 These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens.
857 14530334 Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival.
858 14530334 Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B (RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen.
859 14530334 In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses.
860 14530334 We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs.
861 14530334 These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens.
862 14530334 Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival.
863 14530334 Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B (RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen.
864 14530334 In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses.
865 14530334 We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs.
866 14530334 These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens.
867 14530334 Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival.
868 14593121 Here, we demonstrate that the p50/p65 NF-kappaB transcription factors enhanced the Tat-mediated transcriptional activation of SIVmac239.
869 14605669 Antitumor immunity against bladder cancer induced by ex vivo expression of CD40 ligand gene using retrovirus vector.
870 14605669 The interaction between CD40 ligand (CD40L) and CD40 on antigen-presenting cells is essential for the initiation of antigen-specific T-cell responses.
871 14605669 Antitumor immunity against bladder cancer induced by ex vivo expression of CD40 ligand gene using retrovirus vector.
872 14605669 The interaction between CD40 ligand (CD40L) and CD40 on antigen-presenting cells is essential for the initiation of antigen-specific T-cell responses.
873 14634094 Protection depended on the presence of costimulatory molecules CD80, CD86, and CD40 on the DCs, but surprisingly did not require DCs that could make IL-12 or IL-15.
874 14634094 As NK cells lack memory, we found by depletion that CD4(+) not CD8(+) T cells were required for induction of the NK antitumor response.
875 14634101 Dependent on the DC subset, activation resulted in type 1 IFN production, while both DC subsets produced IL-6 and up-regulated expression of costimulatory molecules CD40 and CD86.
876 14634101 In vivo, however, even upon repeated vaccination with plasmid DNA, priming of OVA-specific CTL and clonal expansion of SIINFEKL-specific CD8 T cells were equal in TLR9-positive and TLR9- or MyD88-negative mice.
877 14645154 In IL-10(-/-) mice, inflammation of the vaccination site was increased with larger numbers of IL-12p40(+), MHC II(+) and CD86(+) cells in the dermal exudate, and was associated with elevated levels of skin-derived IL-12p40 and IL-1beta.
878 14645154 Moreover, such mice had increased numbers of CD4(+) sdLN cells that were CD25(+), CD28(+) or CD152(+) and accessory cells that were CD40(+) or MHC II(+).
879 14645154 Finally, the secretion of IFN-gamma (and IL-12p40) by in vitro cultured sdLN cells was substantially raised in IL-10(-/-) mice, but much reduced in IL-12p40(-/-) mice, resulting in the development of highly polarized T(h)1 and T(h)2 cytokine profiles in the two groups of mice respectively.
880 14645711 An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells.
881 14645711 This adenoviral vector encodes a fusion protein composed of an amino-terminal tumor-associated antigen fragment fused to the CD40 ligand (CD40L).
882 14645711 Subcutaneous injection of an adenoviral vector encoding a fusion protein of the human papillomavirus E7 foreign antigen linked to the CD40L generates CD8+ T cell-dependent immunoresistance to the growth of the E7-positive syngeneic TC-1 cancer cells in C57BL/6 mice for up to 1 year.
883 14645711 We also studied the s.c. injection of a vector carrying the gene for the human MUC-1 (hMUC-1) self-antigen fused to the CD40L.
884 14645711 An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells.
885 14645711 This adenoviral vector encodes a fusion protein composed of an amino-terminal tumor-associated antigen fragment fused to the CD40 ligand (CD40L).
886 14645711 Subcutaneous injection of an adenoviral vector encoding a fusion protein of the human papillomavirus E7 foreign antigen linked to the CD40L generates CD8+ T cell-dependent immunoresistance to the growth of the E7-positive syngeneic TC-1 cancer cells in C57BL/6 mice for up to 1 year.
887 14645711 We also studied the s.c. injection of a vector carrying the gene for the human MUC-1 (hMUC-1) self-antigen fused to the CD40L.
888 14647233 Concurrent delivery of tumor antigens and activation signals to dendritic cells by irradiated CD40 ligand-transfected tumor cells resulted in efficient activation of specific CD8+ T cells.
889 14647233 To improve the efficacy of tumor cell-based and dendritic cell (DC)-based cancer vaccines, this study explored the potential of a new cancer vaccine strategy, that is, the use of CD40 ligand-transfected tumor (CD40L-tumor) cells to simultaneously deliver both tumor-derived antigens (Ag) and maturation stimuli to DCs.
890 14647233 However, during the internalization process, only coculturing with irradiated CD40L-tumor cells resulted in concurrent, optimal DC maturation and production of proinflammatory chemokines and pro-Th1 cytokines, such as IL-6, IL-8, IL-12, IFN-gamma, and TNF-alpha.
891 14647233 Concurrent delivery of tumor antigens and activation signals to dendritic cells by irradiated CD40 ligand-transfected tumor cells resulted in efficient activation of specific CD8+ T cells.
892 14647233 To improve the efficacy of tumor cell-based and dendritic cell (DC)-based cancer vaccines, this study explored the potential of a new cancer vaccine strategy, that is, the use of CD40 ligand-transfected tumor (CD40L-tumor) cells to simultaneously deliver both tumor-derived antigens (Ag) and maturation stimuli to DCs.
893 14647233 However, during the internalization process, only coculturing with irradiated CD40L-tumor cells resulted in concurrent, optimal DC maturation and production of proinflammatory chemokines and pro-Th1 cytokines, such as IL-6, IL-8, IL-12, IFN-gamma, and TNF-alpha.
894 14662831 Cutting edge: a potent adjuvant effect of ligand to receptor activator of NF-kappa B gene for inducing antigen-specific CD8+ T cell response by DNA and viral vector vaccination.
895 14662831 The ligand to receptor activator of NF-kappaB (RANK-L)/RANK interaction has been implicated in CD40 ligand/CD40-independent T cell priming by dendritic cells.
896 14662831 In this report, we show that the coadministration of the RANK-L gene with a Trypanosoma cruzi gene markedly enhances the induction of Trypanosoma Ag-specific CD8(+) T cells and improves the DNA vaccine efficacy.
897 14662831 A similarly potent adjuvant effect of the RANK-L gene on the induction of Ag-specific CD8(+) T cells was also observed when recombinant influenza virus expressing murine malaria Ag was used as an immunogen.
898 14662831 Our results demonstrated, for the first time, the potent immunostimulatory effect of the RANK-L gene to improve the CD8(+) T cell-mediated immunity against infectious agents.
899 14662838 Depletion experiments showed that CD8(+), but not CD4(+), T lymphocytes were crucial for the antitumor activity of the vaccines.
900 14662838 Adjuvant activity of CD40 agonists thus seems to be relevant to enhance the CD8(+) T cell-dependent response in tumor-bearing hosts, suggesting that sustaining tumor-specific T lymphocyte survival in subjects undergoing vaccination might be a key event in the successful vaccination with weak tumor Ags.
901 14670336 Several immunomodulatory functions have been reported for Nef, including down-regulation of CD4 and class I MHC in T-lymphocytes, and the ability to enhance viral transmission from macrophages and dendritic cells (DC) to T-lymphocytes.
902 14670336 In this study, HIV-1 (SF2 strain) Nef was expressed in human monocyte-derived dendritic cells, using an adenovirus based delivery system.
903 14670336 Nef expression resulted in decreased CD4 levels, but no change to class I MHC, and no impairment in the ability of DC to stimulate recall PPD responses, mixed leukocyte responses, or hepatitis B-specific CD8 responses.
904 14670336 The adenovirus vector itself stimulated a strong recall CD4 response in all individuals tested, and also induced up-regulation of class I MHC, CD86 and CD40 on the dendritic cell surface.
905 14671117 Divergent regions contain gene families, which overall comprise over 49% of the CNPV genome and include genes encoding 51 proteins containing ankyrin repeats, 26 N1R/p28-like proteins, and potential immunomodulatory proteins, including those similar to transforming growth factor beta and beta-nerve growth factor.
906 14671117 CNPV genes lacking homologues in FWPV encode proteins similar to ubiquitin, interleukin-10-like proteins, tumor necrosis factor receptor, PIR1 RNA phosphatase, thioredoxin binding protein, MyD116 domain proteins, circovirus Rep proteins, and the nucleotide metabolism proteins thymidylate kinase and ribonucleotide reductase small subunit.
907 14673108 Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1alpha, and tumor necrosis factor alpha by the dendritic cells.
908 14673108 Further, vaccinating mice with eVLPs activated CD4+ and CD8+ T cells, as well as CD19+ B cells.
909 14696096 Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand.
910 14696096 The interaction between the CD40 ligand (CD40L) and CD40 on antigen-presenting cells (APCs) is critical in promoting humoral and cellular immune responses.
911 14696096 The soluble Id-CD40L fusion protein retained CD40 binding activity and stimulated CD80 and CD86 upregulation and interleukin (IL)-12 production by macrophages.
912 14696096 Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand.
913 14696096 The interaction between the CD40 ligand (CD40L) and CD40 on antigen-presenting cells (APCs) is critical in promoting humoral and cellular immune responses.
914 14696096 The soluble Id-CD40L fusion protein retained CD40 binding activity and stimulated CD80 and CD86 upregulation and interleukin (IL)-12 production by macrophages.
915 14696096 Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand.
916 14696096 The interaction between the CD40 ligand (CD40L) and CD40 on antigen-presenting cells (APCs) is critical in promoting humoral and cellular immune responses.
917 14696096 The soluble Id-CD40L fusion protein retained CD40 binding activity and stimulated CD80 and CD86 upregulation and interleukin (IL)-12 production by macrophages.
918 14971031 Dendritic cells generated in the presence of GM-CSF plus IL-15 prime potent CD8+ Tc1 responses in vivo.
919 14971031 DC progenitors can be stimulated to differentiate into immature DC by various growth factors, including GM-CSF and IL-4.
920 14971031 Here we show that IL-15, in combination with GM-CSF, is a growth factor for murine DC.
921 14971031 Murine bone marrow cells, depleted of T cells, B cells, I-A+ cells and Gr-1+ granulocytes, and cultured in the presence of GM-CSF plus IL-15 (IL-15 DC), yielded DC expressing high levels of CD11c and MHC class II molecules, as well as CD11b.
922 14971031 These cells expressed significant levels of CD40, CD80 and CD86, and could stimulate allogeneic CD4+ T cells efficiently.
923 14971031 Interestingly, IL-15 DC were far superior to DC generated with GM-CSF plus IL-4 in stimulating allogeneic CD8+ T cells in vitro.
924 14971031 Consistent with this, IL-15 DC induced much more potent antigen-specific CD8+ T cell responses with high levels of Th1 cytokines in vivo, compared to DC generated with GM-CSF plus IL-4, or with GM-CSF plus TGF-beta, or with GM-CSF alone.
925 14971031 Together, these data suggest that IL-15 promotes the development of DC, which induce potent Th1 and Tc1 responses in vivo.
926 14977976 Furthermore, the treatment of DNA-vaccinated CD4(-/-) mice with an anti-CD8 or anti-gamma interferon (IFN-gamma) antibody significantly reduced the effect of immunization, and neither IFN-gamma(-/-) nor tumor necrosis factor receptor-deficient mice were protected by DNA immunization; therefore, the primary vaccine-induced protective mechanism in these immune-deficient mice likely involves the secretion of cytokines from activated CD8 cells.
927 14991620 In vitro stimulation of immature murine DC with MALP-2 resulted in the induction of maturation with up-regulated expression of MHC class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules.
928 14991620 MALP-2 also enhances the secretion of cytokines (IL-1alpha, IL-6 and IL-12), and increases DC stimulatory activity on naive and antigen-specific T cells.
929 14991620 Further studies demonstrated that MALP-2 treatment of DC results in a dose-dependent shift from the protein pattern of proteasomes to immunoproteasomes (up-regulation of LMP2, LMP7 and MECL1), which correlates with an increased proteolytic activity.
930 14996827 OX40 (CD134), a membrane-bound member of the tumor necrosis factor-receptor superfamily, is expressed primarily on activated CD4(+) T cells.
931 14999431 The vaccine used mature DCs (CD1a+++, CD40++, CD80++, CD83+, and CD86+++) generated from peripheral blood monocytes in the presence of GM-CSF and IL-4.
932 14999431 After 7 days, DCs were matured with a defined cocktail of cytokines (IL-1+IL-6+TNF-alpha+PGE2) and simultaneously pulsed with lysates of heterologous melanoma cell lines, for 2 days.
933 15004163 Nasal Flt3 ligand cDNA elicits CD11c+CD8+ dendritic cells for enhanced mucosal immunity.
934 15004163 In addition, significant levels of OVA-specific CD4+ T cell proliferative responses and OVA-induced IL-4 and IL-2 production were noted in spleen and cervical lymph nodes.
935 15004163 Further, marked increases in FL protein occurred in the nasal lamina propria and submandibular glands and the frequencies of CD11c+CD8+ dendritic cells (DCs) significantly increased in the mucosal tissues.
936 15004163 Moreover, these DCs expressed high levels of CD40, CD80, CD86, and MHC class II molecules.
937 15007094 Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN.
938 15007094 Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10-20-fold greater than the use of either agonist alone.
939 15007094 Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)gamma production and an enhanced secondary response to antigenic challenge.
940 15007094 The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNgamma, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN.
941 15007094 Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN.
942 15007094 Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10-20-fold greater than the use of either agonist alone.
943 15007094 Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)gamma production and an enhanced secondary response to antigenic challenge.
944 15007094 The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNgamma, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN.
945 15007094 Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN.
946 15007094 Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10-20-fold greater than the use of either agonist alone.
947 15007094 Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)gamma production and an enhanced secondary response to antigenic challenge.
948 15007094 The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNgamma, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN.
949 15007094 Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN.
950 15007094 Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10-20-fold greater than the use of either agonist alone.
951 15007094 Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)gamma production and an enhanced secondary response to antigenic challenge.
952 15007094 The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNgamma, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN.
953 15010228 However, live bacteria induced greater up-regulation of the expression of CD40 and CD86 than killed bacteria.
954 15010228 Live bacteria also induced greater up-regulation of transcription for IL-6, IL-12 and GM-CSF than killed bacteria as measured by quantitative RT-PCR.
955 15011756 According to the research group of Shortman, experimental results suggest a "dual" DC differentiation model, demonstrating the existence of both myeloid-derived (with characteristic IF: CD11b+, CD11c+, CD8alpha- and DEC205+) and lymphoid-derived DCs (showing CD11b- CD11c-, CD8alpha+ and DEC205+ IF).
956 15011756 Most of the DCs express immunocytochemically detectable antigens like: S-100, CD1a, CD40 receptor, adhesion molecules (ICAM-1 or CD54, LFA-1 and LFA-3), integrins (CD11a, CD11c and CD18), CD45, CD54, co-stimulatory molecules (B7-1 or CD80, B7-2 or CD86), F418, MHC class I and II and DEC-205, multilectin receptor, immunostimulatory cytokine (IL-12) and, of course, Fc and complement receptors.
957 15019294 CD14-positive cells cultured in the presence of PSK significantly increased the expression of HLA class II antigen and CD40; significantly increased the number and expression of CD80-, CD86- and CD83-positive cells; decreased Fluorescein isothiocyanate (FITC)-dextran uptake, augmented IL-12 production; augmented the allogeneic mixed lymphocyte reaction; and induced antigen-specific cytotoxicity.
958 15067316 Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication.
959 15067316 In vivo blockade of CD28 and CD40 T cell costimulation pathways during acute simian immunodeficiency virus (SIV) infection of rhesus macaques was performed to assess the relative contributions of CD4+ T cells, CD8+ T cells, and Ab responses in modulating SIV replication and disease progression.
960 15067316 Transient administration of CTLA4-Ig and anti-CD40L mAb to SIV-infected rhesus macaques resulted in dramatic inhibition of the generation of both SIV-specific cellular and humoral immune responses.
961 15067316 Acute levels of proliferating CD8+ T cells were associated with early control of SIV viremia but did not predict ensuing set point viremia or survival.
962 15067316 The level of in vivo CD4+ T cell proliferation during acute SIV infection correlated with concomitant peak levels of SIV plasma viremia, whereas measures of in vivo CD4+ T cell proliferation that extended into chronic infection correlated with lower SIV viral load and increased survival.
963 15067316 These results suggest that proliferating CD4+ T cells function both as sources of virus production and as antiviral effectors and that increased levels of CD4+ T cell proliferation during SIV infections reflect antigen-driven antiviral responses rather than a compensatory homeostatic response.
964 15067316 These results highlight the interrelated actions of CD4+ and CD8+ T cell responses in vivo that modulate SIV replication and pathogenesis.
965 15085174 In both cases, antigen-specific CD4+ and CD8+ T cells were detectable after vaccination.
966 15085174 Analysis of DC from Flt-3L-treated mice revealed an immature phenotype with low or absent expression levels of CD80, CD86 and CD40.
967 15103504 In these studies, we demonstrate that exogenous soluble LIGHT or soluble CD40 ligand (CD40L) can promote monocyte-derived dendritic cell maturation in vitro by the up-regulation of CD86, CD80, CD83, and HLA-DR antigen expression.
968 15103504 However, upon induction of maturation by LIGHT or CD40L, the expression of costimulatory and HLA-DR molecules is comparable between DCs from MDS and normal subjects.
969 15103504 Exogenous LIGHT- and CD40L-stimulated mature DCs (mDCs) also displayed increased antigen presentation to autologous T lymphocytes (tetanus toxin) or allogeneic T lymphocytes in mixed lymphocyte reactions.
970 15103504 DCs matured by LIGHT showed increased secretion of IL-6, IL-12p75, and TNF-alpha, but not IL-1beta.
971 15103504 We conclude that both LIGHT and CD40L are immunoregulating factors that induce monocyte-derived iDCs from MDS patients to undergo maturation resulting in increased antigen presentation and T-cell activation.
972 15120002 The in vivo adjuvant properties of N. meningitidis wild-type and mutant LPS was found to correlate with induction of co-stimulatory molecules, in particular CD80 and CD40, and with IL-12 production by LPS-stimulated bone marrow-derived BALB/c dendritic cells in vitro.
973 15128786 Both vectors induced IL-12 and TNF-alpha, but only Lm-LLO-E7 induced IL-2 production by DCs.
974 15128786 Lm-LLO-E7 also induced significantly higher levels of MHC class II molecules, CD40, and B7 costimulatory molecules (CD86, B7-H1, and B7-DC) on DCs than Lm-E7.
975 15128786 A similar shift is also observed for B7-H1 and B7-DC molecules.
976 15128817 Bone marrow-derived DC (BMDC) that had been activated by TNF-alpha or CD40 ligation were not able to induce protection against leishmaniasis in susceptible BALB/c mice.
977 15147576 Modulation of immune responses to bovine herpesvirus-1 in cattle by immunization with a DNA vaccine encoding glycoprotein D as a fusion protein with bovine CD154.
978 15147576 The objective of this study was to determine whether a DNA vaccine encoding bovine CD154 linked to a truncated version of bovine herpesvirus-1 (BHV-1) glycoprotein D (tgD-CD154) induces enhanced tgD-specific immune responses in cattle.
979 15147576 In vitro characterization demonstrated that tgD and tgD-CD154 both bind to cultured bovine B cells, whereas only tgD-CD154 induces interleukin-4-dependent proliferation, suggesting that tgD-CD154 specifically binds the CD40 receptor and induces receptor signalling.
980 15162438 RNA interference technology has been used to modulate dendritic cell (DC) function by targeting the expression of genes such as IL-12 and NF-kappa B.
981 15162438 Inhibition of IL-10 by siRNA was accompanied by increased CD40 expression and IL-12 production after maturation, which endowed DC with the ability to significantly enhance allogeneic T cell proliferation.
982 15162438 IL-10 siRNA transfection did not affect MHC class II, CD86, CD83, or CD54 expression in mature DC.
983 15162438 To further test the ability of IL-10 siRNA-treated DC to induce a T cell response, naive CD4 T cells were stimulated by autologous DC pulsed with KLH.
984 15162438 The results indicated that IL-10 siRNA-transfected DC enhanced Th1 responses by increasing IFN-gamma and decreasing IL-4 production.
985 15181282 CD137 (4-1BB), is an inducible T-cell costimulatory receptor and a member of the tumor necrosis factor receptor (TNFR) superfamily.
986 15181282 The natural counter receptor for CD137 is 4-1BB ligand, a member of the TNF superfamily that is weakly expressed on naïve or resting B cells, macrophages, and DCs.
987 15181282 In T cells CD137-induced signals lead to the recruitment of TRAF family members and activation of several kinases, including ASK-1, MKK, MAPK3/ MAPK4, p38, and JNK/SAPK.
988 15181282 Kinase activation is then followed by the activation and nuclear translocation of several transcription factors, including ATF-2, Jun, and NF-kappaB.
989 15181282 In addition to augmenting suboptimal TCR-induced proliferation, CD137-mediated signaling protects T cells, and in particular, CD8+ T cells from activation-induced cell death (AICD).
990 15189567 NF-kappaB p50 facilitates neutrophil accumulation during LPS-induced pulmonary inflammation.
991 15203918 CD11c (approximately 90%), MHC-II (approximately 70%), CD86 (approximately 20%), CD83 (approximately 5%), CD80 (approximately 40%), CD40 (approximately 40%), and CCR7 (approximately 5%).
992 15207780 Vaccination with OVA-CT-pulsed DC concurrently induced strong CTL in vitro activity and anti-E.G7 tumor protection in vivo in WT, NK-depleted and CD4-deficient mice as well as in IL-12-/- and IFN-gamma-/- mice but not in CD8-deficient mice.
993 15207780 Importantly, activation of CTL by OVA-CT-pulsed DC was dependent on CT-induced activation of adenylate cyclase and increased cAMP production by DC associated with increased expression of MHC class I and co-stimulatory molecules (CD80, CD86 and CD40).
994 15258598 Macrophages and dendritic cells from MyD88-deficient mice stimulated in vitro with BCG mycobacterial antigens produced very low levels of proinflammatory cytokines, while the expression of costimulatory molecules such as CD40 and CD86 was preserved.
995 15258598 Interestingly, the infection was controlled in liver and spleen and there was efficient systemic T-cell priming with high IFNgamma production by CD4+ splenic T cells in MyD88-deficient mice.
996 15258598 Lung infiltrating cells showed IFNgamma production by pulmonary CD4+ T cells upon specific restimulation, and a reduced capacity to produce nitric oxide and IL-10.
997 15259007 Removal of the stratum corneum increased expression of MHC class II, CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to migrate.
998 15259031 Two peptides differing by five residues from the reference p572 (p49 and p50) were more effective than p572 in inducing CTL cross-reacting with p572 in HLA A2.1-transgenic mice.
999 15270693 However, the C-terminal portion (amino acids 359-610) stimulates the production of CC chemokines, IL-12 (interleukin-12), TNFalpha(tumour necrosis factor alpha), NO and maturation of dendritic cells and also functions as an adjuvant in the induction of immune responses.
1000 15270693 Since the receptor for HSP70 is CD40, which with its CD40 ligand constitutes a major co-stimulatory pathway in the interaction between antigen-presenting cells and T-cells, HSP70 may function as an alternative ligand to CD40L.
1001 15291346 CD40 ligand (CD40L) was shown to be a promising molecule for immunotherapy of B-CLL playing a critical role in immune activation.
1002 15308378 Coculture of mouse splenic adherent cells with ovalbumin (OVA)-specific Th1 clone (42-6A) cells in the presence of PS-liposomes encapsulating OVA resulted in high levels of IL-12 and IFN-gamma productions compared with those of positively charged or neutral liposomes.
1003 15308378 IL-12 and IFN-gamma productions were dose-dependent on antigens in PS-liposomes.
1004 15308378 IL-12 production, but not IFN-gamma, was completely inhibited by the addition of anti-CD40L mAb.
1005 15308378 These results indicate that PS-liposomes encapsulating antigens could enhance antigen-dependent IL-12 production through the interaction between CD40 on macrophage/dendritic cells and CD40L on 42-6A cells.
1006 15315856 Nasal immunization of mice with ovalbumin (OVA) plus the Stx1-B or mStx1 induced OVA-specific serum IgG and mucosal IgA responses.
1007 15315856 IgG subclass analysis revealed that mStx1 and Stx1-B as mucosal adjuvants supported Ag-specific IgG1 followed by IgG2b Abs.
1008 15315856 The co-administration of either mStx1 or Stx1-B with OVA enhanced the production of IL-4, IL-5, IL-6 and IL-10 with low IFN-gamma, by OVA-specific CD4+ T cells.
1009 15315856 To better elucidate the mechanisms underlying mStx1's and Stx1-B's adjuvant activity, we next sought to examine whether or not dendritic cells (DC) residing in the nasopharyngeal-associated lymphoreticular tissue (NALT) were activated by nasal administration of Stx1-B or mStx1.
1010 15315856 We found that mice nasally administered with Stx1-B or mStx1 showed an up-regulation in the expression of CD80, CD86 and especially CD40 on NALT DCs.
1011 15315856 Taken together, these results suggest that non-toxic Stx derivatives could be effective mucosal adjuvants for the induction of Th2-type, CD4+ T cell mediated, antigen-specific mucosal IgA and systemic IgG Ab responses, and that they likely owe their adjuvant activity to the up-regulation of co-stimulatory molecules including CD80, CD86 and CD40 on NALT DCs.
1012 15315856 Nasal immunization of mice with ovalbumin (OVA) plus the Stx1-B or mStx1 induced OVA-specific serum IgG and mucosal IgA responses.
1013 15315856 IgG subclass analysis revealed that mStx1 and Stx1-B as mucosal adjuvants supported Ag-specific IgG1 followed by IgG2b Abs.
1014 15315856 The co-administration of either mStx1 or Stx1-B with OVA enhanced the production of IL-4, IL-5, IL-6 and IL-10 with low IFN-gamma, by OVA-specific CD4+ T cells.
1015 15315856 To better elucidate the mechanisms underlying mStx1's and Stx1-B's adjuvant activity, we next sought to examine whether or not dendritic cells (DC) residing in the nasopharyngeal-associated lymphoreticular tissue (NALT) were activated by nasal administration of Stx1-B or mStx1.
1016 15315856 We found that mice nasally administered with Stx1-B or mStx1 showed an up-regulation in the expression of CD80, CD86 and especially CD40 on NALT DCs.
1017 15315856 Taken together, these results suggest that non-toxic Stx derivatives could be effective mucosal adjuvants for the induction of Th2-type, CD4+ T cell mediated, antigen-specific mucosal IgA and systemic IgG Ab responses, and that they likely owe their adjuvant activity to the up-regulation of co-stimulatory molecules including CD80, CD86 and CD40 on NALT DCs.
1018 15322175 In this study, we present a new vaccine design, with Ag covalently conjugated to solid core nano-beads of narrowly defined size (0.04-0.05 microm) that localize to dendritic cells (DEC205(+) CD40(+), CD86(+)) in draining lymph nodes, inducing high levels of IFN-gamma production (CD8 T cells: precursor frequencies 1/5000 to 1/1000) and high Ab titers in mice.
1019 15336548 TgHSP70 induced the maturation of human monocyte-derived dendritic cells as determined by increased levels of surface markers, namely, CD40, CD80, CD86, and HLA-DR.
1020 15336548 TgHSP70 also stimulated extracellular signal-regulated kinase and p38 kinase pathways in DCs, and TgHSP70-induced IL-12 production was inhibited by SB203580 but not by PD98059, thus indicating the role of p38 kinase in the maturation of DCs by TgHSP70.
1021 15364431 Here, we show that BCG infection of monocytes causes their differentiation into mature dendritic cells (DCs) lacking CD1 molecules expression, coupled with suboptimal up-regulation of HLA class II, CD80 and CD40 molecules and a marked unresponsiveness to lipopolysaccharide stimulation.
1022 15389286 Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.
1023 15389286 In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone.
1024 15389286 In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs.
1025 15389286 In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs.
1026 15389286 However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD.
1027 15456078 We found that lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased levels of CD40, CD80, MHC II and CD54 at the cell surface.
1028 15475310 Non-specific immune response genes such as NK, Kupffer cell receptor, MIP1-alpha and Mx1 protein gene were observed to be up-regulated by the VHSV G-protein DNA vaccine at 1 and 3 days post-immunization.
1029 15475310 Also, specific immune-related genes including the CD20 receptor, CD8 alpha chain, CD40 and B lymphocyte cell adhesion molecule were also up-regulated during that time.
1030 15481142 After culture with clinical grade GM-CSF and IL-13, OM-197 at 20 microg/ml efficiently induced CD83+ Mo-DC.
1031 15481142 In comparison to immature Mo-DC that were derived by culture with GM-CSF and IL-13 only, CD40, CD80, CD86, HLA-ABC and HLA-DR molecules were up-regulated upon OM-197 or LPS treatment similarly.
1032 15481142 No significant difference in IFN-gamma quantification was shown between naive CD4+ T cells stimulated by LPS- or OM-197-Mo-DC suggesting that OM-197-Mo-DC can drive naive T cells towards a Th1 response profile that was mainly independent of IL-12 secretion.
1033 15531030 Incubation of immature human PBMC-derived DCs with SHIV VLPs for 48 h resulted in the significant up-regulation of CD40, CD80, CD83, CD54, CD86, HLA-A, B, C and HLA-DR, DP, DQ molecules on activated DC CD11c+ subpopulations.
1034 15531030 SHIV VLPs efficiently stimulated DCs to release IL-12, IFN-gamma and TNF-alpha.
1035 15536147 Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes.
1036 15536147 CD40 ligand is an accessory signal for T-cell activation and can overcome T-cell anergy.
1037 15536147 Transfer of CD40L and OX40L was observed in all and was followed by the up-regulation of B7-1 and B7-2.
1038 15536147 The culture of CD40L/OX40L-expressing B-CLL cells with autologous T cells generated CD4+/CD8+ cytotoxic T-cell lines, which secreted interferon-gamma (IFN-gamma) and granzyme-B/perforin in response to autologous, but not to allogeneic, B-CLL cells or to autologous T-cell blasts.
1039 15536147 Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes.
1040 15536147 CD40 ligand is an accessory signal for T-cell activation and can overcome T-cell anergy.
1041 15536147 Transfer of CD40L and OX40L was observed in all and was followed by the up-regulation of B7-1 and B7-2.
1042 15536147 The culture of CD40L/OX40L-expressing B-CLL cells with autologous T cells generated CD4+/CD8+ cytotoxic T-cell lines, which secreted interferon-gamma (IFN-gamma) and granzyme-B/perforin in response to autologous, but not to allogeneic, B-CLL cells or to autologous T-cell blasts.
1043 15565183 Intratumoral administration of immature dendritic cells following the adenovirus vector encoding CD40 ligand elicits significant regression of established myeloma.
1044 15565183 The potent antitumor effect produced by the combination therapy correlated with high expression of MHC, costimulatory and Fas molecules on J558 cells, which was derived from CD40L transgene expression.
1045 15565183 Finally, in vivo depletion experimentation suggested both CD4+ and CD8+ T cells were involved in mediating the antitumor immune responses of combined treatment of AdVCD40L and iDCs, with CD8+ T cells being the major effector.
1046 15582662 Rescue of memory CD8+ T cell reactivity in peptide/TLR9 ligand immunization by codelivery of cytokines or CD40 ligation.
1047 15582662 Here, we show that immunization of mice with SSIEFARL peptide (immunodominant epitope in glycoprotein B of herpes simplex virus type 1, aa498-505) combined with TLR9 ligand in the absence of helper CD4(+) T cell activation generates a functionally impaired CD8(+) T cell memory response.
1048 15582662 Codelivery of IL-12, IL-15, or anti-CD40 together with MHC class-I-restricted peptide combined with TLR9 ligand at inception of immunization resulted in generation of memory CD8(+) T cells that were several fold less compromised than immunization with peptide alone.
1049 15582662 Furthermore, administration of either plasmid DNA encoding IL-15 or anti-CD40 mAb but not rIL-12 during the memory phase restored the reactivity of memory CD8(+) T cells.
1050 15585869 APCs expressing the activation markers MHC class II, CD80, and CD40 increased in number in the lung.
1051 15585869 LTK63 treatment increased the pathogen-specific IgA response in the nasal mucosa and simultaneously decreased inflammatory cytokine production (IFN-gamma and TNF-alpha) after infection.
1052 15585869 The number of activated CD8(+)CD44(+) T cells and the respiratory syncytial virus- or influenza-specific CD8-proliferative responses increased, although the total inflammatory infiltrate was reduced.
1053 15599405 Activation of invariant CD1d-dependent NK T cells (iNKT cells) in vivo through administration of the glycolipid ligand alpha-galactosylceramide (alpha-GalCer) or the sphingosine-truncated alpha-GalCer analog OCH leads to CD40 signaling as well as the release of soluble molecules including type 1 and gamma interferons that contribute to DC maturation.
1054 15599405 The adjuvant activity of alpha-GalCer enhances both priming and boosting of CD8(+) T cells to coadministered peptide or protein antigens, including a peptide encoding the clinically relevant, HLA-A2-restricted epitope of the human tumor antigen NY-ESO-1.
1055 15650233 Here we shall review the work carried out in our lab in recent years and show that NB cells express tumor-associated antigens, such as MAGE-3, but lack constitutive expression of costimulatory molecules and surface HLA class I and II molecules.
1056 15650233 Notably, in vitro experiments with NB cell lines demonstrated that surface HLA class I molecules and the CD40 costimulatory molecule were upregulated following cell incubation with recombinant interferon-gamma.
1057 15650233 Interaction of CD40 with recombinant CD40 ligand induced apoptosis of NB cells through a caspase 8-dependent mechanism.
1058 15650233 Here we shall review the work carried out in our lab in recent years and show that NB cells express tumor-associated antigens, such as MAGE-3, but lack constitutive expression of costimulatory molecules and surface HLA class I and II molecules.
1059 15650233 Notably, in vitro experiments with NB cell lines demonstrated that surface HLA class I molecules and the CD40 costimulatory molecule were upregulated following cell incubation with recombinant interferon-gamma.
1060 15650233 Interaction of CD40 with recombinant CD40 ligand induced apoptosis of NB cells through a caspase 8-dependent mechanism.
1061 15652674 Exposure to proteoliposomes from serogroup B Neisseria meningitidis (PL) induced up-regulation of MHC-II, MHC-I, CD40, CD80 and CD86 expression on the surface of murine bone marrow-derived dendritic cells (DC).
1062 15652674 CD40, CD80 and CD86 were up-regulated on bone marrow-derived macrophages (MPhi) upon stimulation with PL.
1063 15652674 A small increase in the expression of MHC-II, CD40 and CD86, as well as production of IL12(p70), was observed on the cell surface of DC, but not MPhi from LPS-non-responder C3H/HeJ after exposure to PL.
1064 15652674 DC, but not MPhi, incubated with PL containing ovalbumin (PL-OVA) presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas.
1065 15652674 The work also shows the potential of PL as a general system to deliver antigens to DC for presentation to CD4+ and CD8+ T-cells.
1066 15652674 Exposure to proteoliposomes from serogroup B Neisseria meningitidis (PL) induced up-regulation of MHC-II, MHC-I, CD40, CD80 and CD86 expression on the surface of murine bone marrow-derived dendritic cells (DC).
1067 15652674 CD40, CD80 and CD86 were up-regulated on bone marrow-derived macrophages (MPhi) upon stimulation with PL.
1068 15652674 A small increase in the expression of MHC-II, CD40 and CD86, as well as production of IL12(p70), was observed on the cell surface of DC, but not MPhi from LPS-non-responder C3H/HeJ after exposure to PL.
1069 15652674 DC, but not MPhi, incubated with PL containing ovalbumin (PL-OVA) presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas.
1070 15652674 The work also shows the potential of PL as a general system to deliver antigens to DC for presentation to CD4+ and CD8+ T-cells.
1071 15652674 Exposure to proteoliposomes from serogroup B Neisseria meningitidis (PL) induced up-regulation of MHC-II, MHC-I, CD40, CD80 and CD86 expression on the surface of murine bone marrow-derived dendritic cells (DC).
1072 15652674 CD40, CD80 and CD86 were up-regulated on bone marrow-derived macrophages (MPhi) upon stimulation with PL.
1073 15652674 A small increase in the expression of MHC-II, CD40 and CD86, as well as production of IL12(p70), was observed on the cell surface of DC, but not MPhi from LPS-non-responder C3H/HeJ after exposure to PL.
1074 15652674 DC, but not MPhi, incubated with PL containing ovalbumin (PL-OVA) presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas.
1075 15652674 The work also shows the potential of PL as a general system to deliver antigens to DC for presentation to CD4+ and CD8+ T-cells.
1076 15653438 Using one CpG-ODN, DSP30, we observed that it could upregulate not only Toll-like receptor 9 (TLR9) mRNA expression in activated B-cells, but also the early expression of CD69 followed by the sequential expression of CD80, CD86 and the nuclear factor (NF)-kappaB pathway.
1077 15653438 Furthermore, mRNA expression of certain B-cell-derived cytokines was influenced by exposure to DSP30, with a strong upregulation of interleukin 6 (IL-6) and downregulation of IL1-beta.
1078 15653438 Stimulation of B-cells, co-stimulated with IL-2, IL-10 and soluble CD40 ligand (sCD40L) with different CpG-ODNs, had differing effects on the terminal differentiation in vitro of B-cells into immunoglobulin-secreting cells.
1079 15664921 Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32.
1080 15664921 Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion.
1081 15664921 MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation.
1082 15683451 In a clinical phase I/II study, monocyte-derived DC were generated in vitro utilizing granulocyte macrophage colony-stimulating factor and rh-interleukin-4 (IL-4) and used for cancer immunotherapy.
1083 15683451 Polyriboinosinic polyribocytidylic acid (Poly I:C) + tumour necrosis factor-alpha (TNF-alpha) induced significant IL-12 p70 secretion, which was increased after addition of a decoy IL-10 receptor.
1084 15683451 The lymph node homing chemokine receptor CCR-7 expression was induced by TNF-alpha + IL-1beta + IL-6 + prostaglandin E2 but was not induced by Poly I:C + TNF-alpha.
1085 15683451 In general, DC from patients had an intermediate maturity phenotype with a significantly higher expression of CD40 and CD54 compared with healthy donors.
1086 15710900 Lactobacillus-exposed MDCs up-regulated HLA-DR, CD83, CD40, CD80, and CD86 and secreted high levels of IL-12 and IL-18, but not IL-10.
1087 15710900 IL-12 was sustained in MDCs exposed to all three Lactobacillus species in the presence of LPS from Escherichia coli, whereas LPS-induced IL-10 was greatly inhibited.
1088 15710900 MDCs activated with lactobacilli clearly skewed CD4(+) and CD8(+) T cells to T helper 1 and Tc1 polarization, as evidenced by secretion of IFN-gamma, but not IL-4 or IL-13.
1089 15725957 Co-incubation of immature DCs with ghosts resulted in decreased expression of CD1a, CD80, and CD83 molecules, while addition of maturation mix (TNF-alpha, IL-1 beta, IL-6, and PGE2) to the cultures enhanced expression of these molecules.
1090 15725957 No marked changes were observed in the expression of the CD11c, CD40, and CD86 surface molecules.
1091 15730392 Mature dendritic cells differentiated in the presence of interferon-beta and interleukin-3 prime functional antigen-specific CD8 T cells.
1092 15730392 Monocytes incubated in the presence of interferon (IFN)-beta and interleukin (IL)-3 give rise to a distinct type of DCs (IFN-beta/IL-3 DCs) that are particularly efficient at eliciting IFN-gamma and IL-5 production by allogeneic helper T cells.
1093 15730392 We assessed the capacity of this new type of DCs to prime antigen-specific naive CD8(+) T cells and compared them to the conventional DCs differentiated in the presence of granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4 (GM-CSF/IL-4 DCs).
1094 15730392 We demonstrate that IFN-beta/IL-3 DCs matured by TLR3 or CD40 ligation efficiently prime Melan-A(26-35)-specific CD8(+) T cells in vitro, at a similar level as GM-CSF/IL-4 DCs.
1095 15730392 Activated antigen-specific CD8(+) T cells produced IFN-gamma and displayed potent cytotoxic activity against peptide-pulsed target cells.
1096 15730392 Expansion of CD8(+) T cell numbers was generally higher following priming with CD40-L than with polyinosinic-polycytidylic acid (poly I:C) matured DCs.
1097 15730392 These data indicate that IFN-beta/IL-3 DCs represent a promising cell population for the immunotherapy of cancer.
1098 15731055 DC exposed to live EBs acquired a mature DC morphology; expressed high levels of major histocompatibility complex (MHC) class II, CD80, CD86, CD40, and ICAM-1; produced elevated amounts of interleukin-12 and tumor necrosis factor alpha; and were efficiently recognized by Chlamydia-specific CD4+ T cells.
1099 15731055 In contrast, UV-EB-pulsed DC expressed low levels of CD40 and CD86 but displayed high levels of MHC class II, ICAM-1, and CD80; secreted low levels of proinflammatory cytokines; and exhibited reduced recognition by Chlamydia-specific CD4+ T cells.
1100 15731055 DC exposed to live EBs acquired a mature DC morphology; expressed high levels of major histocompatibility complex (MHC) class II, CD80, CD86, CD40, and ICAM-1; produced elevated amounts of interleukin-12 and tumor necrosis factor alpha; and were efficiently recognized by Chlamydia-specific CD4+ T cells.
1101 15731055 In contrast, UV-EB-pulsed DC expressed low levels of CD40 and CD86 but displayed high levels of MHC class II, ICAM-1, and CD80; secreted low levels of proinflammatory cytokines; and exhibited reduced recognition by Chlamydia-specific CD4+ T cells.
1102 15735048 CD4(+) Treg cells do not secrete interleukin (IL)-10 and transforming growth factor beta cytokines but express CD25, the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), and Forkhead Box P3 (Foxp3), and are capable of suppressing the proliferative responses of naive CD4(+) and CD8(+) T cells to stimulation with mitogenic anti-CD3 antibody.
1103 15735048 Importantly, these Treg cells suppress IL-2 secretion by CD4(+) effector T cells specific for either EBNA1 or a melanoma antigen, suggesting that these CD4(+) Treg cells induce immune suppression.
1104 15753654 Here, the efficiency of DC transduction by Ad vectors retargeted to DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) was studied and compared to that of Ad vectors retargeted through CD40.
1105 15753654 A comparable and significant enhancement of gene transfer to monocyte derived DCs (MDDCs) was accomplished by means of an Ad vector harboring the Fc-binding domain of Staphylococcus aureus protein A in combination with antibodies to DC-SIGN or to CD40 or with fused complexes of human Ig-Fc with their natural ligands, i.e., ICAM-3 or CD40L, respectively.
1106 15753654 Whereas CD40-targeted Ad transduction resulted in a more profound phenotypic DC maturation, DC-SIGN- and CD40-targeted Ad both induced similar levels of IL-12 secretion.
1107 15753654 Here, the efficiency of DC transduction by Ad vectors retargeted to DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) was studied and compared to that of Ad vectors retargeted through CD40.
1108 15753654 A comparable and significant enhancement of gene transfer to monocyte derived DCs (MDDCs) was accomplished by means of an Ad vector harboring the Fc-binding domain of Staphylococcus aureus protein A in combination with antibodies to DC-SIGN or to CD40 or with fused complexes of human Ig-Fc with their natural ligands, i.e., ICAM-3 or CD40L, respectively.
1109 15753654 Whereas CD40-targeted Ad transduction resulted in a more profound phenotypic DC maturation, DC-SIGN- and CD40-targeted Ad both induced similar levels of IL-12 secretion.
1110 15753654 Here, the efficiency of DC transduction by Ad vectors retargeted to DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) was studied and compared to that of Ad vectors retargeted through CD40.
1111 15753654 A comparable and significant enhancement of gene transfer to monocyte derived DCs (MDDCs) was accomplished by means of an Ad vector harboring the Fc-binding domain of Staphylococcus aureus protein A in combination with antibodies to DC-SIGN or to CD40 or with fused complexes of human Ig-Fc with their natural ligands, i.e., ICAM-3 or CD40L, respectively.
1112 15753654 Whereas CD40-targeted Ad transduction resulted in a more profound phenotypic DC maturation, DC-SIGN- and CD40-targeted Ad both induced similar levels of IL-12 secretion.
1113 15787742 Murine bone marrow-derived dendritic cells (DC) can be generated by culture in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) alone or GM-CSF in conjunction with interleukin-4 (IL-4).
1114 15787742 Also, the four culture conditions generated CD11c+ DC with comparable levels of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86 expression, with the exception of cells cultured under serum-free conditions in the absence of IL-4, which displayed suboptimal levels of these markers.
1115 15787742 However, both DC populations displayed a similar capacity to take up fluorescein isothiocyanate (FITC)-albumin by macropinocytosis and FITC-Dextran by the mannose receptor and to secrete IL-12 in response to stimulation with lipopolysaccharide (LPS) or an agonistic anti-CD40 monoclonal antibody.
1116 15787742 Therefore, we conclude that although both DC culture methods result in the production of DC with similar functional abilities, under serum-free conditions, DC cultured in GM-CSF and IL-4 show an increased stimulatory potential over DC cultured in GM-CSF alone.
1117 15812230 Nonreplicating recombinant vaccinia virus expressing CD40 ligand enhances APC capacity to stimulate specific CD4+ and CD8+ T cell responses.
1118 15812230 Recently, we and others have demonstrated, in vitro and in vivo, that coexpression of CD80 and CD86 costimulatory molecules enhances the immunogenic capacity of a recombinant vaccinia virus (rVV) encoding different tumor-associated antigens.
1119 15812230 To further investigate the capacity of these vectors to provide ligands for different costimulatory pathways relevant in the generation of T cell responses, we constructed a recombinant virus (rVV) expressing CD40 ligand or CD154 (CD154rVV).
1120 15812230 Upon binding the CD40 receptor expressed on antigen presenting cells (APC), this molecule, physiologically expressed on activated CD4+ T cells, increases their antigen presentation and immunostimulatory capacities.
1121 15812230 CD154rVV infection of autologous fibroblasts, monocytes, or iDC promoted the expression of a number of cytokines, including GM-CSF, TNF-alpha, and IL-15 in iDC.
1122 15812230 Most importantly, IL-12 p40 gene expression and protein secretion were induced by CD154rVV but not by wild-type VV (WT VV) in either CD14+ cells or iDC, and these effects could be blocked by anti-CD40 monoclonal antibodies.
1123 15812230 Furthermore, phenotypic characterization of CD154rVV infected iDC revealed enhanced expression of CD83 and CD86 surface markers as compared with wild-type vaccinia virus infection.
1124 15812230 However, cytokine genes typically expressed by T cell receptor triggered T cells such as those encoding IL-2 and IFN-gamma, or T cell proliferation, were detectable to a significantly higher extent in CD154rVV infected cultures, as compared with WT VV.
1125 15812230 Activation of specific CD8+ T cells was then investigated using MART-1/Melan-A(27-35) epitope as the model of tumor-associated antigen (TAA).
1126 15812230 Nonreplicating recombinant vaccinia virus expressing CD40 ligand enhances APC capacity to stimulate specific CD4+ and CD8+ T cell responses.
1127 15812230 Recently, we and others have demonstrated, in vitro and in vivo, that coexpression of CD80 and CD86 costimulatory molecules enhances the immunogenic capacity of a recombinant vaccinia virus (rVV) encoding different tumor-associated antigens.
1128 15812230 To further investigate the capacity of these vectors to provide ligands for different costimulatory pathways relevant in the generation of T cell responses, we constructed a recombinant virus (rVV) expressing CD40 ligand or CD154 (CD154rVV).
1129 15812230 Upon binding the CD40 receptor expressed on antigen presenting cells (APC), this molecule, physiologically expressed on activated CD4+ T cells, increases their antigen presentation and immunostimulatory capacities.
1130 15812230 CD154rVV infection of autologous fibroblasts, monocytes, or iDC promoted the expression of a number of cytokines, including GM-CSF, TNF-alpha, and IL-15 in iDC.
1131 15812230 Most importantly, IL-12 p40 gene expression and protein secretion were induced by CD154rVV but not by wild-type VV (WT VV) in either CD14+ cells or iDC, and these effects could be blocked by anti-CD40 monoclonal antibodies.
1132 15812230 Furthermore, phenotypic characterization of CD154rVV infected iDC revealed enhanced expression of CD83 and CD86 surface markers as compared with wild-type vaccinia virus infection.
1133 15812230 However, cytokine genes typically expressed by T cell receptor triggered T cells such as those encoding IL-2 and IFN-gamma, or T cell proliferation, were detectable to a significantly higher extent in CD154rVV infected cultures, as compared with WT VV.
1134 15812230 Activation of specific CD8+ T cells was then investigated using MART-1/Melan-A(27-35) epitope as the model of tumor-associated antigen (TAA).
1135 15812230 Nonreplicating recombinant vaccinia virus expressing CD40 ligand enhances APC capacity to stimulate specific CD4+ and CD8+ T cell responses.
1136 15812230 Recently, we and others have demonstrated, in vitro and in vivo, that coexpression of CD80 and CD86 costimulatory molecules enhances the immunogenic capacity of a recombinant vaccinia virus (rVV) encoding different tumor-associated antigens.
1137 15812230 To further investigate the capacity of these vectors to provide ligands for different costimulatory pathways relevant in the generation of T cell responses, we constructed a recombinant virus (rVV) expressing CD40 ligand or CD154 (CD154rVV).
1138 15812230 Upon binding the CD40 receptor expressed on antigen presenting cells (APC), this molecule, physiologically expressed on activated CD4+ T cells, increases their antigen presentation and immunostimulatory capacities.
1139 15812230 CD154rVV infection of autologous fibroblasts, monocytes, or iDC promoted the expression of a number of cytokines, including GM-CSF, TNF-alpha, and IL-15 in iDC.
1140 15812230 Most importantly, IL-12 p40 gene expression and protein secretion were induced by CD154rVV but not by wild-type VV (WT VV) in either CD14+ cells or iDC, and these effects could be blocked by anti-CD40 monoclonal antibodies.
1141 15812230 Furthermore, phenotypic characterization of CD154rVV infected iDC revealed enhanced expression of CD83 and CD86 surface markers as compared with wild-type vaccinia virus infection.
1142 15812230 However, cytokine genes typically expressed by T cell receptor triggered T cells such as those encoding IL-2 and IFN-gamma, or T cell proliferation, were detectable to a significantly higher extent in CD154rVV infected cultures, as compared with WT VV.
1143 15812230 Activation of specific CD8+ T cells was then investigated using MART-1/Melan-A(27-35) epitope as the model of tumor-associated antigen (TAA).
1144 15814713 IL-10 deficiency caused early maturation and activation of pulsed DC (i.e., high CD11c, CD40, CD80, CD83, CD86, IL-1, IL-12, and the T cell-attracting chemokine CCL27/CTACK) and consequently an enhanced ability to process and present Ags for a rapid and robust T cell activation.
1145 15814713 Supporting comparative proteomics revealed further that IL-10 deficient DC possess specific immunobiological properties, e.g., the T cell-attracting chemokine CCL27/CTACK, calcium-dependent protein kinase, and the IL-1/IL-12 inducer, NKR-P1A (CD161), which differentiated them immunologically from wild-type DC that express molecules relating to anti-inflammatory, differentiative, and metabolic processes, e.g., the anti-IL-12 molecule peroxisome proliferator-activated receptor-alpha and thymidine kinase.
1146 15837371 However, CD40mAbs are effective adjuvants in CD154-/- mice, indicating that the antibodies are able to provide the CD40 stimulus to B cells which is naturally lacking in these mice.
1147 15867395 Increased NK activity was associated with a raise in CD3-CD56+ NK and/or CD3+CD56+ NK-like T cells, displaying enhanced expression of NKG2D and/or NKp46 receptors.
1148 15867395 Up-regulated expression of CD83 and CD40 and increased interleukin-12 release on stimulation were observed in CD14+ cells from post-HSP96 peripheral blood mononuclear cells, suggesting an indirect pathway of NK stimulation by HSP96-activated monocytes.
1149 15877606 Monocyte-derived dendritic cells (mDC), the most frequently applied DC subset in clinical studies, which can be obtained easily from peripheral blood monocytes after incubation with GM-CSF and IL-4, have not been clearly demonstrated to be activated by CpG oligodeoxynucleotides (ODN).
1150 15877606 However, we did not observe increased expression of maturation-associated and functionally relevant surface antigens (CD14, HLA-DR, CD40, CD83, CD80 and CD86), significant secretion of IL-12 and IFN-alpha in culture supernatant, or enhanced antitumour activation of cytokine-induced killer cells.
1151 15879130 Activated B cells exhibited increased expression of activation markers and ligands that are critical for cross-talk with T cells (CD19, CD25, CD80, CD86, MHC I, MHC II, and CD40).
1152 15891775 The DCs expressed CD11c, CD11b, and the costimulatory molecules CD40, CD80 and CD86, characteristic of mature DCs.
1153 15905566 The correct interaction of a costimulatory molecule such as CD40L with its contrareceptor CD40 expressed on the membrane of professional APCs, provides transmembrane signaling that leads to APC activation.
1154 15905566 Therefore, we investigated whether a novel intranasal delivery of immune-reconstituted influenza virosomes (IRIV), assembled with the CD40L gene (CD40L/IRIV), could be used to improve protective immunity and the Ag-specific CTL response against carcinoembryonic Ag (CEA) generated with a novel vaccine constituted of IRIV assembled with the CEA gene (CEA/IRIV).
1155 15905566 Our results suggest that CD40L/IRIV was able to augment CEA-specific CTL activity and CEA-specific protective immunity induced by CEA/IRIV most likely through the induction of a CTL response associated with a Th1 phenotype.
1156 15905566 In conclusion, we provide evidence that CD40L/IRIV, by acting through the CD40L/CD40 signaling pathway, acts as an immune-adjuvant that could increase the efficacy of a CEA-specific cancer vaccine, which could provide an efficacious new strategy for cancer therapy.
1157 15905566 The correct interaction of a costimulatory molecule such as CD40L with its contrareceptor CD40 expressed on the membrane of professional APCs, provides transmembrane signaling that leads to APC activation.
1158 15905566 Therefore, we investigated whether a novel intranasal delivery of immune-reconstituted influenza virosomes (IRIV), assembled with the CD40L gene (CD40L/IRIV), could be used to improve protective immunity and the Ag-specific CTL response against carcinoembryonic Ag (CEA) generated with a novel vaccine constituted of IRIV assembled with the CEA gene (CEA/IRIV).
1159 15905566 Our results suggest that CD40L/IRIV was able to augment CEA-specific CTL activity and CEA-specific protective immunity induced by CEA/IRIV most likely through the induction of a CTL response associated with a Th1 phenotype.
1160 15905566 In conclusion, we provide evidence that CD40L/IRIV, by acting through the CD40L/CD40 signaling pathway, acts as an immune-adjuvant that could increase the efficacy of a CEA-specific cancer vaccine, which could provide an efficacious new strategy for cancer therapy.
1161 15934782 Previously, we have reported that an Ad5 vector targeted to CD40 via genetic capsid incorporation of CD40L achieves selective transduction of DC in vitro.
1162 15936851 In this study, we demonstrated that WKYMVm enhanced the surface expression of CD80, but not that of CD40, CD86 and MHC class II, on mouse bone marrow-derived dendritic cells which is one of the essential costimulatory signals for the induction of immune responses.
1163 15936851 Furthermore, when WKYMVm was codelivered with HIV, HBV and Influenza DNA vaccines, WKYMVm selectively enhanced the vaccine-induced CD8(+) T cell responses in a dose-dependent manner, in terms of IFN-gamma secretion and cytolytic activity.
1164 15944268 Immunization with HIV-1 Gag protein conjugated to a TLR7/8 agonist results in the generation of HIV-1 Gag-specific Th1 and CD8+ T cell responses.
1165 15944268 Injection of R-848 and CpG oligodeoxynucleotides alone enhanced the innate immune responses in vivo as demonstrated by high serum levels of inflammatory cytokines, including IL-12p70 and IFN-alpha, and increased expression of CD80, CD86, and CD40 on CD11c(+) dendritic cells.
1166 15944268 By contrast, R-848 was a relatively poor adjuvant for inducing primary Th1 or CD8(+) T cell responses when administered with HIV-1 Gag protein.
1167 15944268 However, when a TLR7/8 agonist structurally and functionally similar to R-848 was conjugated to HIV-1 Gag protein both Th1 and CD8(+) T cells responses were elicited as determined by intracellular cytokine and tetramer staining.
1168 15955282 The aim of this study was to determine the immunomodulatory effects of IL-12, IL-18 and CD154 (CD40 ligand, CD40L) in DNA-vaccination against the classical swine fever virus.
1169 15955282 Four recombinant plasmids were constructed including the CSFV coding region for the glycoprotein gp55/E2 alone or together with porcine IL-12, IL-18 or CD154 genes.
1170 15955282 This study showed that co-delivery of IL-18 and CD154 induced an earlier appearance of serum antibodies, reduced B-cell deficiency after infection and protected pigs against a lethal CSFV infection.
1171 15956570 The cytopathic effect (CPE) seen with some subgroups of avian sarcoma and leukosis virus (ASLV) is associated with viral Env activation of the death-promoting activity of TVB (a tumor necrosis factor receptor-related receptor that is most closely related to mammalian TNF-related apoptosis-inducing ligand [TRAIL] receptors) and with viral superinfection leading to unintegrated viral DNA (UVD) accumulation, which is presumed to activate a cellular DNA damage response.
1172 15968107 In this chapter, we describe the design and methods for cloning a cDNA gene coding for the mouse CD40L molecule and for construction of the expression vector pcDNA-CD40L, as well as the methods for generation of engineered myeloma cells J558/CD40L expressing CD40 ligand.
1173 15972497 Our results showed that StxB1 and mStx1, but not native Stx1 (nStx1), resulted in enhanced expression of CD86, CD40, and major histocompatibility complex (MHC) class II molecules and, to some extent, also enhanced the expression of CD80 on bone marrow-derived DCs.
1174 15972497 StxB1-treated DCs exhibited an increase in tumor necrosis factor alpha and interleukin-12 (IL-12) production, a stimulation of DO11.10 T-cell proliferation, and the production of both Th1 and Th2 cytokines, including gamma interferon (IFN-gamma), IL-4, IL-5, IL-6, and IL-10.
1175 15972497 When mice were given StxB1 subcutaneously, the levels of CD80, CD86, and CD40, as well as MHC class II expression by splenic DCs, were enhanced.
1176 15972497 OVA-specific CD4+ T cells isolated from mice immunized with OVA plus mStx1 or StxB1 produced IFN-gamma, IL-4, IL-5, IL-6, and IL-10, indicating that mStx1 and StxB1 elicit both Th1- and Th2-type responses.
1177 15972497 Our results showed that StxB1 and mStx1, but not native Stx1 (nStx1), resulted in enhanced expression of CD86, CD40, and major histocompatibility complex (MHC) class II molecules and, to some extent, also enhanced the expression of CD80 on bone marrow-derived DCs.
1178 15972497 StxB1-treated DCs exhibited an increase in tumor necrosis factor alpha and interleukin-12 (IL-12) production, a stimulation of DO11.10 T-cell proliferation, and the production of both Th1 and Th2 cytokines, including gamma interferon (IFN-gamma), IL-4, IL-5, IL-6, and IL-10.
1179 15972497 When mice were given StxB1 subcutaneously, the levels of CD80, CD86, and CD40, as well as MHC class II expression by splenic DCs, were enhanced.
1180 15972497 OVA-specific CD4+ T cells isolated from mice immunized with OVA plus mStx1 or StxB1 produced IFN-gamma, IL-4, IL-5, IL-6, and IL-10, indicating that mStx1 and StxB1 elicit both Th1- and Th2-type responses.
1181 16037410 Dendritic cells differentiated in the presence of IFN-{beta} and IL-3 are potent inducers of an antigen-specific CD8+ T cell response.
1182 16037410 Classically, mature monocyte-derived DC are generated in vitro in the presence of interleukin (IL)-4, granulocyte macrophage-colony stimulating factor, and inflammatory cytokines (G4-DC).
1183 16037410 Recently, it has been described that DC can also be generated in the presence of IL-3 and interferon (IFN)-beta and that these DC are efficiently matured using polyriboinosinic polyribocytidylic acid (I3-DC).
1184 16037410 Phenotypic characterization of the DC revealed differences in the expression of the monocyte marker CD14 and the maturation marker CD83.
1185 16037410 Low expression of CD14 and high expression of CD83 characterized G4-DC, whereas I3-DC displayed intermediate expression of CD14 and CD83.
1186 16037410 Upon CD40 ligation, G4-DC produced lower amounts of IFN-alpha and pulmonary and activation-regulated chemokine, similar amounts of IL-6, macrophage-inflammatory protein (MIP)-1alpha, and MIP-1beta, and higher amounts of IL-12 p70, tumor necrosis factor alpha, and MIP-3beta than I3-DC.
1187 16037410 Finally, in vitro stimulations showed that fresh and frozen peptide-loaded I3-DC are more potent inducers of Melan-A-specific CD8(+) T cell responses than G4-DC.
1188 16037638 RAd alone hardly infected PDC (2%) while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25% CD83 positive cells).
1189 16037638 Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFNgamma producing CTL was reduced by 75% compared to stimulation with peptide loaded PDC).
1190 16061684 CD4+ T cells are able to promote tumor growth through inhibition of tumor-specific CD8+ T-cell responses in tumor-bearing hosts.
1191 16061684 We analyzed the contribution of the CD4+ T-cell population to the induction or suppression of tumor-specific CD8+ T cells in a tumor model in which eradication of tumors crucially depends on CD8+ T cell-mediated immunity.
1192 16061684 Vaccine-mediated induction of protective antitumor immunity in the preventive setting (i.e., before tumor challenge) was CD4+ T cell dependent because depletion of this T-cell subset prevented CD8+ T-cell induction.
1193 16061684 In contrast, depletion of CD4+ cells in mice bearing established E1A+ tumors empowered the mice to raise strong CD8+ T-cell immunity capable of tumor eradication without the need for tumor-specific vaccination.
1194 16061684 Spontaneous eradication of tumors, which had initially grown out, was similarly observed in MHC class II-deficient mice, supporting the notion that the tumor-bearing mice harbor a class II MHC-restricted CD4+ T-cell subset capable of suppressing a tumor-specific CD8+ T-cell immune response.
1195 16061684 The deleterious effects of the presence of CD4+ T cells in tumor-bearing hosts could be overcome by CD40-triggering or injection of CpG.
1196 16107864 DNA vaccination with an insulin construct and a chimeric protein binding to both CTLA4 and CD40 ameliorates type 1 diabetes in NOD mice.
1197 16107864 This mutant B7.1 binds CTLA4 but not CD28.
1198 16107864 We report that young NOD mice immunized with mbPPI along with mB7.1/CD40L DNA vectors significantly reduced diabetes incidence while treatment with CTLA4/IgG1 exacerbated diabetes.
1199 16113842 Furthermore, B-CLL-DCs generated from the 2 CLL subgroups up-regulated MHC-II, CD80, CD86, CD83, CD40, and CD54 and down-regulated CD206 in response to stimulation with a cocktail of cytokines (CyC) and secreted increased levels of tumor necrosis factor alpha, interleukin (IL)-8, IL-6, IL-12 (p70), and RANTES in a manner typical of mature normal-DCs.
1200 16155029 New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab.
1201 16155029 New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab.
1202 16155029 These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor.
1203 16158496 Dendritic cells treated with chitosan or PLGA (agarose to a lesser extent) films increased expression levels of CD86, CD40, and HLA-DQ, compared to control iDCs, similar to LPS-matured DCs, whereas DCs treated with alginate or hyaluronic acid films decreased their expression levels of these same molecules.
1204 16176850 Regulation of CD4 T cell memory by OX40 (CD134).
1205 16176850 Recent advances in studies of T cell memory have implicated the tumor-necrosis-factor receptor (TNFR) family member, OX40 (CD134), as a key co-stimulatory molecule involved in the regulation of CD4 memory T cells.
1206 16177330 Transfection of Trypanosoma cruzi with host CD40 ligand results in improved control of parasite infection.
1207 16177330 We have previously shown that infection by Trypanosoma cruzi, a parasitic protozoan, is reduced by injection of CD40 ligand (CD40L)-transfected 3T3 fibroblasts (D.
1208 16177330 Transfection of Trypanosoma cruzi with host CD40 ligand results in improved control of parasite infection.
1209 16177330 We have previously shown that infection by Trypanosoma cruzi, a parasitic protozoan, is reduced by injection of CD40 ligand (CD40L)-transfected 3T3 fibroblasts (D.
1210 16186817 Recently activated, but not resting, CD4(+) T cells express CD154, providing costimulatory signals to B cells and antigen-presenting cells (APCs).
1211 16186817 Therefore, de novo CD154 expression after stimulation identifies antigen-specific CD4(+) T cells.
1212 16186817 Using this assay, we found that stimulated cells expressing tumor necrosis factor (TNF)-alpha, interleukin (IL)-2 or interferon (IFN)-gamma were predominantly CD154(+).
1213 16186817 For vaccine- or pathogen-specific responses, we found substantial heterogeneity in expression of CD154 and cytokines, suggesting previously unrecognized diversity in abilities of responding cells to stimulate APCs through CD40.
1214 16196281 DCs were generated from mouse bone marrow in the presence of rmGM-CSF (3.3 ng/mL) and rmIL-4 (1.3 ng/mL) and detected by FACS, and then transfected with the recombinant adenovirus encoding mutant k-ras gene.
1215 16196281 BmDCs highly expressed B7-1 (80%), B7-2 (77%), MHC II (70%), CD11c (65%), CD40 (70%) and CD54 (96%) with FACS, and no significant difference in the expression was observed before and after the transfection (P > 0.05).
1216 16196281 The DCs transfected by mutant k-ras gene could significantly stimulate lymphocytes proliferation as compared with those transfected by Ad-c or non-modified DCs (P < 0.05).
1217 16196281 DC vaccine transfected by mutant k-ras gene could induce CTL activity against Lewis lung cancer, but not against B16.
1218 16203783 Responses to human CD40 ligand/human interleukin-2 autologous cell vaccine in patients with B-cell chronic lymphocytic leukemia.
1219 16207252 A novel CD4-CD8alpha+CD205+CD11b- murine spleen dendritic cell line: establishment, characterization and functional analysis in a model of vaccination to toxoplasmosis.
1220 16207252 These cells display similar morphology, phenotype and activity to CD4(-)CD8alpha(+)CD205(+)CD11b(-) DCs purified ex vivo.
1221 16207252 Toxoplasma gondii antigen was shown to be taken up by these cells and to increase class I and class II major histocompatibility complex (MHC), CD40, CD80 and CD86 surface expression.
1222 16207252 The SRDC or CD4(-)CD8alpha(+)CD205(+)CD11b(-) DC line can be expected to be a very useful tool for immunobiology studies of DC.
1223 16272340 In the present study, we used the mouse-specific OPV ectromelia virus and mice deficient in CD40, B cells, or CD8+ T cells and adoptive transfers of CD8+ T or B lymphocytes to show that the protection afforded by CD8+ T cells is incomplete.
1224 16279537 The generation of ripe dendrite cells (DC) of marrow origin was obtained with the use of the vaccine Immunovac-BN-4, an immunomodulator of microbial origin, as well as Klebsiella pneumoniae LPS and TNF-alpha, as ripening inducers.
1225 16279537 The immunophenotype of cells altered from CD34+, CD38-, CD40-, CD80-, CD86-, MHC I-, MHC II-, F4/80- to CD34-, CD38+, CD40+, CD80+, MHC I+, MHC II+, F4/ 80(low).
1226 16279537 In culture medium with ripe DC the levels of such cytokines as IL-1b, IL-6, IL-12, IFN-gamma, TNF-alpha significantly increased and the production of IL-4 decreased.
1227 16279537 The content of IL-2 and IL-10 remained unchanged.
1228 16297159 When dendritic cells were stimulated simultaneously by CD40 ligation and IFN-alpha2a, the production of interleukin (IL)-10 and IL-12 was increased.
1229 16297159 The production of IFN-gamma and IL-5 by the responder naive T cells was also amplified in response to IFN-alpha2a-treated DCs.
1230 16297159 Furthermore, IL-12 production by IFN-alpha2a-treated DCs was enhanced further in the presence of anti-IL-10 antibody.
1231 16297159 Under these circumstances, IFN-alpha2a did not modify the DC phenotype, and the production of IL-10/IL-12 and IFN-gamma/IL-5 by DCs and by DC-stimulated naive T cells, respectively, was inhibited compared to the effects on DCs treated with maturation factors alone.
1232 16300869 Here, we investigated the possibility to enhance the CD8 response against the human and mouse shared TERT(572Y) HLA-A*0201 restricted modified cryptic peptide by using ODN-CpG as adjuvant.
1233 16300869 Those cells and especially the CD11c+ CD11b- CD8a+ lymphoid and the CD11c+ B220+ plasmacytoid dendritic cells were activated as shown by up-regulation of CD40 at their cell surface.
1234 16303787 Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs.
1235 16303787 We demonstrate here that the addition of PGE2 to TNF for the maturation of MoDCs enhanced CD4 and CD8 T cell proliferative responses to neoantigen and recall antigen, and enhanced Th1-type responses.
1236 16303787 The increased stimulatory capacity of MoDCs matured with PGE2 was associated with a fully mature, migratory-type MoDC phenotype and more rapid down-regulation of the expression of inflammatory chemokines, with up-regulated expression of the constitutive chemokines TARC and MDC.
1237 16303787 In addition, although MoDCs matured with TNF and PGE2 selectively produced the inhibitory IL-12p40 subunit at steady state, they were able to produce the bioactive IL-12p70 heterodimer after stimulation with CD40 ligand and/or IFN-gamma.
1238 16303787 Despite increased IL-6 mRNA expression, MoDCs matured with PGE2 did not overcome the suppressive effects of CD4+ CD25+ T cells in allogeneic mixed lymphocyte reactions.
1239 16308571 Here, we show that plasmid DNA vaccination with a cassette encoding antigen (OVA) and a second cassette encoding full-length CD40 ligand (CD40L), a molecule expressed on activated CD4+ T lymphocytes and critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and Tc1 CD8+ T cell responses in CD4-deficient mice.
1240 16308571 To investigate whether this approach leads to CD4+ T cell-independent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia, we used serum from mice vaccinated with PC-pulsed, CD40L-modified DCs to immunoprecipitate PC antigens.
1241 16308571 CD4-deficient mice receiving DNA vaccines encoding Kexin and CD40L showed significantly higher anti-PC IgG titers as well as opsonic killing of PC compared with those vaccinated with Kexin alone.
1242 16315029 Immature bone marrow derived DC grown in vitro with IL-4 and GM-CSF were pulsed with B16-CD44.
1243 16315029 After 48 h of pulsing, maturation of DC was demonstrated by production of IL-12 and upregulation of CD80 and CD40 expression.
1244 16315029 To test the efficacy of vaccination with DC+B16-CD44, mice were vaccinated subcutaneously Lymphocytes from mice vaccinated with DC+B16-CD44 produced IFN-gamma in response to B16 melanoma lysates as well as an MHC class I restricted B16 melanoma-associated peptide, indicating B16 specific CD8 T cell activation.
1245 16330534 Compared with blood counterparts, lymph monocytes expressed lower levels of CD40, and granulocytes expressed higher levels of CD80.
1246 16361412 NS3 protein was efficiently transduced into DCs and treatment of DCs with CpG ODN induced phenotypic maturation and specifically increased the expression of CD40.
1247 16394001 The intranasal administration of HA-Surfacten stimulated the expression of MHC class II, CD40, and CD86 molecules in the CD11c-positive cells isolated from the nasal mucosa, but not the expression of cells from the lungs or spleens.
1248 16420604 Both DEN2 and LAV2 increased the expression of the phenotypic markers CD80, CD86, CD40, CD1a, HLA ABC and CD83, demonstrating cellular activation.
1249 16420604 Stimulated dendritic cells produced tumor necrosis factor-alpha in particular, and, to a lower extent, interleukin 6.
1250 16421599 Taking advantage of the HSVQuik system, we constructed three oncolytic HSV vectors that express mouse IL4, CD40 ligand and 6CK, respectively.
1251 16425257 The enhanced immunity is due to the increase of CD11c(+) and CD11c(+) CD40(+) double positive dendritic cells in mice that received immune-modulators, GM-CSF and anti-CD40.
1252 16439533 Multimeric soluble CD40 ligand and GITR ligand as adjuvants for human immunodeficiency virus DNA vaccines.
1253 16439533 CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant, but it has been difficult to use because it is normally expressed as a trimeric membrane molecule.
1254 16439533 Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion with the body of surfactant protein D was used to produce the 4-trimer form.
1255 16439533 These CD40L-augmented DNA vaccines elicited strong CD8(+) T-cell responses but did not elicit significant CD4(+) T-cell or antibody responses.
1256 16439533 To test the applicability of the multimeric fusion protein approach to other TNFSFs, a 4-trimer construct for the ligand of glucocorticoid-induced TNF family-related receptor (GITR) was also prepared.
1257 16439533 Multimeric soluble GITR ligand (GITRL) augmented the CD8(+) T-cell, CD4(+) T-cell, and antibody responses to DNA vaccination.
1258 16439533 In summary, multimeric CD40L and GITRL are new adjuvants for DNA vaccines.
1259 16439533 Multimeric soluble CD40 ligand and GITR ligand as adjuvants for human immunodeficiency virus DNA vaccines.
1260 16439533 CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant, but it has been difficult to use because it is normally expressed as a trimeric membrane molecule.
1261 16439533 Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion with the body of surfactant protein D was used to produce the 4-trimer form.
1262 16439533 These CD40L-augmented DNA vaccines elicited strong CD8(+) T-cell responses but did not elicit significant CD4(+) T-cell or antibody responses.
1263 16439533 To test the applicability of the multimeric fusion protein approach to other TNFSFs, a 4-trimer construct for the ligand of glucocorticoid-induced TNF family-related receptor (GITR) was also prepared.
1264 16439533 Multimeric soluble GITR ligand (GITRL) augmented the CD8(+) T-cell, CD4(+) T-cell, and antibody responses to DNA vaccination.
1265 16439533 In summary, multimeric CD40L and GITRL are new adjuvants for DNA vaccines.
1266 16443827 C274 induced macaque CD20(+) B cells to proliferate more strongly than CD40 ligand or CpG-B ISS-ODN.
1267 16443827 Increased expression of CD40, CD80, and CD86 by B cells was apparent within 24 h of exposure to C274 and persisted for up to 1 week.
1268 16443827 C274-stimulated, B cell-enriched and peripheral blood mononuclear cell suspensions from naïve and immunodeficiency virus-infected monkeys secreted several cytokines [e.g., interleukin (IL)-3, IL-6, IL-12, interferon-alpha] and chemokines [e.g., monocyte chemoattractant protein-1/CC chemokine ligand 2 (CCL2), macrophage-inflammatory protein-1alpha/CCL3, IL-8/CXC chemokine ligand 8].
1269 16443827 C274 induced macaque CD20(+) B cells to proliferate more strongly than CD40 ligand or CpG-B ISS-ODN.
1270 16443827 Increased expression of CD40, CD80, and CD86 by B cells was apparent within 24 h of exposure to C274 and persisted for up to 1 week.
1271 16443827 C274-stimulated, B cell-enriched and peripheral blood mononuclear cell suspensions from naïve and immunodeficiency virus-infected monkeys secreted several cytokines [e.g., interleukin (IL)-3, IL-6, IL-12, interferon-alpha] and chemokines [e.g., monocyte chemoattractant protein-1/CC chemokine ligand 2 (CCL2), macrophage-inflammatory protein-1alpha/CCL3, IL-8/CXC chemokine ligand 8].
1272 16446013 Our results demonstrate that two vaccines can activate DC of chronic HBV infection and healthy control by upregulation CD40 and CD86, high production of IL-12p70 and TNF-alpha.
1273 16455994 In this study, we show that BLS stimulates bone marrow dendritic cells from mice in vitro to up-regulate the levels of costimulatory molecules (CD40, CD80, and CD86) and major histocompatibility class II Ag.
1274 16474127 Our results demonstrate that, in contrast to the rwt virus, rM51R-M virus induced the maturation of myeloid DC (mDC) populations, as indicated by an increase in the surface expression of CD40, CD80, and CD86 as well as the secretion of interleukin-12 (IL-12), IL-6, and type I IFN.
1275 16474127 Our studies also indicated that the production of costimulatory molecules on mDC by rM51R-M virus was dependent on the type I IFN receptor, while maturation induced by this virus was largely independent of MyD88.
1276 16480795 Dendritic cell cross-presentation is credited with the ability of tumor lysate-loaded dendritic cells to prime both CD4 and CD8-specific T-lymphocyte responses, enabling the generation of cancer specific CTL activity without the loading of the classical MHC class I compartment.
1277 16480795 Enhanced recall responses appeared to be influenced by CD40/CD40L signaling, underscoring the importance of T-cell help in the generation and perpetuation of the adaptive immune response.
1278 16491482 Adenovirus-mediated CD40 ligand therapy induces tumor cell apoptosis and systemic immunity in the TRAMP-C2 mouse prostate cancer model.
1279 16493050 Myeloid cells had a CD4+CD11b+CD11c+CD16+CD123(low)HLA-DR- phenotype, expressed myeloperoxidase, and included a population of M-CSFR+ monocyte-lineage committed cells.
1280 16493050 Further culture of myeloid cells in serum-free medium with GM-CSF and IL-4 generated cells that had typical dendritic morphology; expressed high levels of MHC class I and II molecules, CD1a, CD11c, CD80, CD86, DC-SIGN, and CD40; and were capable of Ag processing, triggering naive T cells in MLR, and presenting Ags to specific T cell clones through the MHC class I pathway.
1281 16493050 Incubation of DCs with A23187 calcium ionophore for 48 h induced an expression of mature DC markers CD83 and fascin.
1282 16493050 The combination of GM-CSF with IL-4 provided the best conditions for DC differentiation.
1283 16493050 DCs obtained with GM-CSF and TNF-alpha coexpressed a high level of CD14, and had low stimulatory capacity in MLR.
1284 16499575 These cells can be generated from peripheral blood monocytes cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4).
1285 16499575 We found that 24-h IFN-alpha co-culture of day 7 monocyte-derived DC generated with GM-CSF and IL-4 induces increased numbers of DC positive for CD54 and CD40 together with the co-stimulatory molecule CD80 but not the activation marker CD83.
1286 16499575 Also, IFN-alpha maturation leads to an increase in IP-10 and MCP-1 chemokine secretion, but only a minor increase in IL-12p40 secretion.
1287 16522779 Lactic acid bacteria inducing a weak interleukin-12 and tumor necrosis factor alpha response in human dendritic cells inhibit strongly stimulating lactic acid bacteria but act synergistically with gram-negative bacteria.
1288 16522779 While strains of LAB varied greatly in their capacity to induce interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha), G- strains were consistently weak IL-12 and TNF-alpha inducers.
1289 16522779 Interestingly, we found that when weakly IL-12- and TNF-alpha-inducing LAB and strong IL-12- and TNF-alpha-inducing LAB were mixed, the weakly IL-12- and TNF-alpha-inducing LAB efficiently inhibited otherwise strong IL-12- and TNF-alpha-inducing LAB, yet when weakly IL-12- and TNF-alpha-inducing LAB were mixed with G- bacteria, they synergistically induced IL-12 and TNF-alpha.
1290 16522779 Furthermore, strong IL-12- and TNF-alpha-inducing LAB efficiently up-regulated surface markers (CD40, CD83, CD86, and HLA-DR), which were inhibited by weakly IL-12- and TNF-alpha-inducing LAB.
1291 16522779 All G- bacteria potently up-regulated surface markers; however, these markers were not inhibited by weakly IL-12- and TNF-alpha-inducing LAB.
1292 16530301 The purpose of this article is to review recent advances in adjuvant development using approaches that directly exploit the immune system's own co-stimulatory pathways to exert their function; with a particular emphasis on CD40 and CD28 based therapies.
1293 16585551 Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes.
1294 16585551 We found that intranasal vaccination of NOD mice with plasmid DNA encoding mouse proinsulin II-induced CD4+ T(reg) that suppressed diabetes development, both after adoptive cotransfer with "diabetogenic" spleen cells and after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset.
1295 16585551 In contrast to prototypic CD4+ CD25+ T(reg), CD4+ T(reg) induced by proinsulin DNA were both CD25+ and CD25- and not defined by markers such as glucocorticoid-induced TNFR-related protein (GITR), CD103, or Foxp3.
1296 16585551 However, diabetes was prevented when DNA vaccination was performed under the cover of CD40 ligand blockade, known to prevent priming of CTL by mucosal Ag.
1297 16621190 The VLP induced an increase in expression of CD40, CD80 and CD86 but required an adjuvant, CpG DNA oligo-deoxy nucleotides (ODN) motifs, to enhance these responses.
1298 16622023 Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo.
1299 16622023 We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40(-/-) and CD40L(-/-) mice and analyzing their resistance to reinfection in a murine pulmonary model.
1300 16622023 In the absence of CD40 or CD40L, CD4(+) cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8(+) T1 cells.
1301 16622023 If CD4(+) cells were first eliminated, vaccination of CD40(-/-) and CD40L(-/-) mice restored priming of CD8(+) cells, type 1 cytokine production, and resistance.
1302 16622023 Hence, CD4(+) and CD8(+) cells differ sharply in their requirement for CD40/CD40L interaction during the generation of antifungal immunity.
1303 16622023 Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4(+) cells may impede the priming of CD8(+) cells at the cost of host survival against a lethal infectious disease.
1304 16622023 Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo.
1305 16622023 We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40(-/-) and CD40L(-/-) mice and analyzing their resistance to reinfection in a murine pulmonary model.
1306 16622023 In the absence of CD40 or CD40L, CD4(+) cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8(+) T1 cells.
1307 16622023 If CD4(+) cells were first eliminated, vaccination of CD40(-/-) and CD40L(-/-) mice restored priming of CD8(+) cells, type 1 cytokine production, and resistance.
1308 16622023 Hence, CD4(+) and CD8(+) cells differ sharply in their requirement for CD40/CD40L interaction during the generation of antifungal immunity.
1309 16622023 Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4(+) cells may impede the priming of CD8(+) cells at the cost of host survival against a lethal infectious disease.
1310 16622023 Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo.
1311 16622023 We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40(-/-) and CD40L(-/-) mice and analyzing their resistance to reinfection in a murine pulmonary model.
1312 16622023 In the absence of CD40 or CD40L, CD4(+) cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8(+) T1 cells.
1313 16622023 If CD4(+) cells were first eliminated, vaccination of CD40(-/-) and CD40L(-/-) mice restored priming of CD8(+) cells, type 1 cytokine production, and resistance.
1314 16622023 Hence, CD4(+) and CD8(+) cells differ sharply in their requirement for CD40/CD40L interaction during the generation of antifungal immunity.
1315 16622023 Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4(+) cells may impede the priming of CD8(+) cells at the cost of host survival against a lethal infectious disease.
1316 16622023 Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo.
1317 16622023 We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40(-/-) and CD40L(-/-) mice and analyzing their resistance to reinfection in a murine pulmonary model.
1318 16622023 In the absence of CD40 or CD40L, CD4(+) cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8(+) T1 cells.
1319 16622023 If CD4(+) cells were first eliminated, vaccination of CD40(-/-) and CD40L(-/-) mice restored priming of CD8(+) cells, type 1 cytokine production, and resistance.
1320 16622023 Hence, CD4(+) and CD8(+) cells differ sharply in their requirement for CD40/CD40L interaction during the generation of antifungal immunity.
1321 16622023 Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4(+) cells may impede the priming of CD8(+) cells at the cost of host survival against a lethal infectious disease.
1322 16622023 Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo.
1323 16622023 We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40(-/-) and CD40L(-/-) mice and analyzing their resistance to reinfection in a murine pulmonary model.
1324 16622023 In the absence of CD40 or CD40L, CD4(+) cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8(+) T1 cells.
1325 16622023 If CD4(+) cells were first eliminated, vaccination of CD40(-/-) and CD40L(-/-) mice restored priming of CD8(+) cells, type 1 cytokine production, and resistance.
1326 16622023 Hence, CD4(+) and CD8(+) cells differ sharply in their requirement for CD40/CD40L interaction during the generation of antifungal immunity.
1327 16622023 Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4(+) cells may impede the priming of CD8(+) cells at the cost of host survival against a lethal infectious disease.
1328 16622023 Ligation of CD40 by CD40L on T cells is critical for the induction of these immune responses in vivo.
1329 16622023 We explored the role of CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by immunizing CD40(-/-) and CD40L(-/-) mice and analyzing their resistance to reinfection in a murine pulmonary model.
1330 16622023 In the absence of CD40 or CD40L, CD4(+) cells failed to get primed or produce type 1 cytokine and impaired the generation of CD8(+) T1 cells.
1331 16622023 If CD4(+) cells were first eliminated, vaccination of CD40(-/-) and CD40L(-/-) mice restored priming of CD8(+) cells, type 1 cytokine production, and resistance.
1332 16622023 Hence, CD4(+) and CD8(+) cells differ sharply in their requirement for CD40/CD40L interaction during the generation of antifungal immunity.
1333 16622023 Despite the plasticity of T cell subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4(+) cells may impede the priming of CD8(+) cells at the cost of host survival against a lethal infectious disease.
1334 16637009 We recently described a novel marker combination (CD127 and CD62L) to identify all three major CD8(+) T cell subsets in mice infected with Listeria monocytogenes (L.m.).
1335 16637009 In vivo priming protocols that preferentially induced one of the different CD8(+) T cell subsets demonstrated that predominance of T(EM) (CD40 stimulation) correlated best with effective protection against L.m., whereas generation of neither T(CM) (by immunization with heat-killed L.m.) nor T(EC) (by systemic co-administration of CpG during primary infection) conferred substantial long-term protective immunity.
1336 16651447 We sought to improve on this strategy by combining xenogeneic DNA vaccination with an agonist anti-glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) monoclonal antibody (mAb), DTA-1, which has been shown previously both to costimulate activated effector CD4(+) and CD8(+) T cells and to inhibit the suppressive activity of CD4(+)CD25(+) regulatory T cells.
1337 16651447 We found that ligation of GITR with DTA-1 just before the second, but not the first, of 3 weekly DNA immunizations enhanced primary CD8(+) T-cell responses against the melanoma differentiation antigens gp100 and tyrosinase-related protein 2/dopachrome tautomerase and increased protection from a lethal challenge with B16 melanoma.
1338 16651447 Finally, this effect on vaccine-induced CD8(+) T-cell responses was partially independent of CD4(+) T cells (both helper and regulatory), consistent with a direct costimulatory effect on the effector CD8(+) cells themselves.
1339 16651452 Immunization of stage IV melanoma patients with Melan-A/MART-1 and gp100 peptides plus IFN-alpha results in the activation of specific CD8(+) T cells and monocyte/dendritic cell precursors.
1340 16651452 We have carried out a pilot phase I-II trial to determine the effects of IFN-alpha, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients.
1341 16651452 In five of the seven evaluable patients, a consistent enhancement of CD8(+) T cells recognizing modified and native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was observed.
1342 16651452 In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction.
1343 16651452 An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed.
1344 16651452 Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8(+) T cells.
1345 16708399 We found that HS-Exo, compared with control exosomes derived from the same cells (Exo), contain more HSP60 and HSP90 and increased amounts of molecules involved in immunogenicity including MHC class I, MHC class II, CD40, CD86, RANTES and IL-1beta.
1346 16708399 We further demonstrate that CD8(+) T cells are the predominant T cell subset responsible for the antitumor effect of HS-Exo and that CD4(+) T cells are necessary in the induction phase of tumor rejection in a prophylaxis model.
1347 16750567 Besides TLRs, mRNA for MyD88 and TRAF6, and nuclear translocation of NF-kappaB were enhanced that indicate their involvement in tandem in the activity of porin.
1348 16750567 The protein selectively up-regulated CD80 on the activated MPhi together with MHC class II molecule and CD40, and had no effect on CD86 expression.
1349 16750567 The porin-induced profile of MIP-1alpha, MIP-1beta and RANTES showed strong bias for chemokines correlated with M1 polarization.
1350 16750567 Intracellular expression and release of TNF-alpha and IL-12 in presence of porin was found to be TLR2 and NF-kappaB dependent.
1351 16750567 Induction of TNF-alpha and IL-12 along with the chemokine profile suggests type I polarization of the MPhi that would influence Th1-type response.
1352 16823910 CD40 and CD28 based adjuvants are extremely potent and should avoid the inflammatory side effects induced by most adjuvants.
1353 16823912 DC were incubated with PL resulting in up-regulation of MHC-II, CD40, CD80, and CD86 expression and production of TNFalpha and IL12(p70).
1354 16823912 PL-OVA presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas.
1355 16823912 PL exerts an immunomodulatory effect on DC and is a general system to deliver antigens for presentation to CD4+ and CD8+ T-cells possibly implicated in the induction CD8+ cytotoxic T lymphocytes (CTLs) responses.
1356 16857732 Critical role for serum opsonins and complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in phagocytosis of Francisella tularensis by human dendritic cells (DC): uptake of Francisella leads to activation of immature DC and intracellular survival of the bacteria.
1357 16857732 We demonstrate that complement factor C3-derived opsonins and the major complement receptors expressed by DC, the integrins CR3 (CD11b/CD18) and CR4 (CD11c/CD18), play a critical role in this adhesion-mediated phagocytosis.
1358 16857732 LVS induced proinflammatory cytokine production and up-regulation of costimulatory surface proteins (CD40, CD86, and MHC Class II) on DC but resisted killing.
1359 16857732 Serum-treated LVS rapidly induced (within 6 h) a number of cytokines including IL-10, a potent suppressor of macrophage functions and down-regulator of Th1-like responses and the Th1 response inducer IL-12.
1360 16857732 These results suggest that the simultaneous production of an activating (IL-12, IL-1beta, and TNF-alpha) and a suppressing (IL-10) cytokine profile could contribute to the immunopathogenesis of tularemia.
1361 16884670 Experimental immunotherapy approaches in clinical development include 1) cytokines such as IL-7 and IL-21, 2) cytokine-antibody fusion proteins or immunocytokines, 3) whole tumor cell vaccines, 4) genetically modified tumor cells, 5) heat shock protein vaccines, 6) peptide vaccines, 7) dendritic cells pulsed with tumor antigens, 8) tumor antigen-naked DNA vectors, 9) recombinant viral vectors (either alone or in a prime boost schedule), 10) adoptive transfer of cloned tumor antigen-specific T cells, 11) Toll-like receptor ligands, 12) antagonistic antibodies to the cytotoxic T-lymphocyte antigen 4 (CTLA4, CD152), and 13) activating antibodies to CD40 and CD137 (41-BB).
1362 16889876 Important features for their efficacy include high migratory responsiveness to lymph node-chemokines and most likely their ability to produce bioactive IL-12 p70 upon subsequent contact with CD40 ligand-expressing T-cells.
1363 16889876 The current standard DC-maturation cocktail for clinical trials is inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) combined with prostaglandin E(2) (PGE(2)), inducing phenotypically mature MoDCs with high migratory responsiveness to CCR7 ligands.
1364 16889876 This cocktail does not, however, induce or prime for production of IL-12 p70.
1365 16889876 Addition of IFN-gamma to PGE(2)-containing maturation cocktails has been shown to prime for substantial production of IL-12 p70 by subsequent CD40 ligation, but the impact of IFN-gamma on phenotypic maturation and migratory responsiveness induced by PGE(2)-containing inflammatory stimuli still remains elusive.
1366 16889876 Here, we demonstrate that addition of IFN-gamma to the standard maturation cocktail decreased CCR7 mRNA and down-regulated CCR7 expression on MoDCs in a dose-dependent manner.
1367 16889876 Moreover, addition of IFN-gamma was found to suppress MoDC-migration towards the CCR7-ligands CCL19 and CCL21.
1368 16889876 Important features for their efficacy include high migratory responsiveness to lymph node-chemokines and most likely their ability to produce bioactive IL-12 p70 upon subsequent contact with CD40 ligand-expressing T-cells.
1369 16889876 The current standard DC-maturation cocktail for clinical trials is inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) combined with prostaglandin E(2) (PGE(2)), inducing phenotypically mature MoDCs with high migratory responsiveness to CCR7 ligands.
1370 16889876 This cocktail does not, however, induce or prime for production of IL-12 p70.
1371 16889876 Addition of IFN-gamma to PGE(2)-containing maturation cocktails has been shown to prime for substantial production of IL-12 p70 by subsequent CD40 ligation, but the impact of IFN-gamma on phenotypic maturation and migratory responsiveness induced by PGE(2)-containing inflammatory stimuli still remains elusive.
1372 16889876 Here, we demonstrate that addition of IFN-gamma to the standard maturation cocktail decreased CCR7 mRNA and down-regulated CCR7 expression on MoDCs in a dose-dependent manner.
1373 16889876 Moreover, addition of IFN-gamma was found to suppress MoDC-migration towards the CCR7-ligands CCL19 and CCL21.
1374 16893998 Immunotargeting with CD154 (CD40 ligand) enhances DNA vaccine responses in ducks.
1375 16893998 Engagement of CD154 on activated T cells with CD40 on antigen-presenting cells (APCs) potentiates adaptive immune responses in mammals.
1376 16893998 Thus, targeting of antigens to APCs with CD154 is an effective strategy to enhance DNA vaccine responses not only in mammalian species but also in avian species.
1377 16893998 Immunotargeting with CD154 (CD40 ligand) enhances DNA vaccine responses in ducks.
1378 16893998 Engagement of CD154 on activated T cells with CD40 on antigen-presenting cells (APCs) potentiates adaptive immune responses in mammals.
1379 16893998 Thus, targeting of antigens to APCs with CD154 is an effective strategy to enhance DNA vaccine responses not only in mammalian species but also in avian species.
1380 16917781 BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines.
1381 16917781 Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA(257-264) or OVA(323-339)], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells.
1382 16931603 Molecular adjuvants can be considered in the following groups: TNF superfamily molecules such as CD40 ligand; agonists for TLRs; agonists for NAIP, CIITA, HET-E, TP-1-leucine-rich repeat pathway receptors, such as nucleotide-binding and oligomerization domain (NOD)1, NOD2, and cryopyrin; chemokines; ILs; CSFs; IFNs; alarmins; and purinergic P2X7 receptor agonists.
1383 16931603 Complementing these positively acting agents are strategies to reduce the immunosuppressive effects of CD4+CD25+ regulatory T cells and negatively acting factors such as TGF-beta, IL-10, suppressor of cytokine signaling 1, and programmed cell death-1 using neutralizing antibodies, antisense, and small interfering RNA.
1384 16960116 Treatment of human monocytes with S. gordonii but not latex beads induced a clear up-regulation of CD83, CD40, CD80, and CD54 and the down-regulation of CD14.
1385 16960116 Furthermore, bacterial treatment stimulated an increased expression of Toll-like receptor 5 (TLR5), TLR6, and TLR7, production of the proinflammatory cytokines tumor necrosis factor alpha and interleukin 1 beta, and reduction of the phagocytic activity.
1386 16966494 This report demonstrates that the B box domain induces phenotypic maturation of murine bone marrow-derived dendritic cells (BM-DCs) as evidenced by increased CD86, CD40 and MHC-II expression.
1387 16966494 The B box domain enhanced secretion of pro-inflammatory cytokines and chemokines: IL-1beta, IL-2, IL-5, IL-8, IL-12 and tumor necrosis factor (TNF)-alpha, but not IL-6 and IL-10.
1388 16966494 Furthermore, four peptides whose sequences correspond to different regions of HMGB1 induced production of IL-1beta, IL-2 and IL-12 (p70), but not IL-10 and IL-6 in mouse BM-DCs.
1389 16966494 Interestingly, these peptides differed in their capacity to induce TNF-alpha, IL-5, IL-18 and IL-8.
1390 16971806 Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients.
1391 16971806 These immature DCs can be rapidly activated by soluble CD40 ligand (CD40L).
1392 16971806 Flt3 ligand-mobilized DCs (FLDCs) were isolated, activated with CD40L, loaded with antigenic peptides from influenza matrix protein, hepatitis B core antigen, NY-ESO-1, MAGE-A4, and MAGE-A10, and injected into patients with resected melanoma.
1393 16971806 Overnight culture with soluble CD40L caused marked up-regulation of activation markers (CD83 and HLA-DR).
1394 16971806 Blood dendritic cells generated with Flt3 ligand and CD40 ligand prime CD8+ T cells efficiently in cancer patients.
1395 16971806 These immature DCs can be rapidly activated by soluble CD40 ligand (CD40L).
1396 16971806 Flt3 ligand-mobilized DCs (FLDCs) were isolated, activated with CD40L, loaded with antigenic peptides from influenza matrix protein, hepatitis B core antigen, NY-ESO-1, MAGE-A4, and MAGE-A10, and injected into patients with resected melanoma.
1397 16971806 Overnight culture with soluble CD40L caused marked up-regulation of activation markers (CD83 and HLA-DR).
1398 16971810 Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.
1399 16971810 DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand.
1400 16971810 Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen.
1401 16971810 Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides.
1402 16971810 In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred.
1403 16988005 Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro.
1404 16988005 CD40 ligand (CD40L) and GITR ligand (glucocorticoid-induced tumor necrosis factor receptor-related protein ligand [GITRL]) are tumor necrosis factor superfamily molecules that can be used as vaccine adjuvants.
1405 16988005 In a previous human immunodeficiency virus (HIV) DNA vaccine study in mice, we found that plasmids expressing multimeric soluble forms of trimeric CD40L (i.e., many trimers) were stronger activators of CD8(+) T-cell responses than were single-trimer soluble forms or the natural membrane-bound molecule.
1406 16988005 With human cells, four-trimer macaque GITRL costimulated CD4(+) T-cell proliferation and abrogated the immunosuppressive effects of CD4(+) CD25(+) regulatory T cells on a mixed leukocyte reaction.
1407 16988005 Macaque multimeric soluble CD40 ligand and GITR ligand constructs are immunostimulatory molecules in vitro.
1408 16988005 CD40 ligand (CD40L) and GITR ligand (glucocorticoid-induced tumor necrosis factor receptor-related protein ligand [GITRL]) are tumor necrosis factor superfamily molecules that can be used as vaccine adjuvants.
1409 16988005 In a previous human immunodeficiency virus (HIV) DNA vaccine study in mice, we found that plasmids expressing multimeric soluble forms of trimeric CD40L (i.e., many trimers) were stronger activators of CD8(+) T-cell responses than were single-trimer soluble forms or the natural membrane-bound molecule.
1410 16988005 With human cells, four-trimer macaque GITRL costimulated CD4(+) T-cell proliferation and abrogated the immunosuppressive effects of CD4(+) CD25(+) regulatory T cells on a mixed leukocyte reaction.
1411 17048271 BM-derived macrophages and DC displayed enhanced expression of costimulatory molecules (CD40 and CD86) and increased production of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-12p40) and nitric oxide after infection.
1412 17073943 In this study, we showed that ovalbumin (OVA) protein-pulsed DC (DC(OVA))-derived EXO (EXO(OVA)) displayed MHC class I-OVA I peptide (pMHC I) complexes, CD11c, CD40, CD80, CCR7, DEC205, Toll-like receptor 4 (TLR4), TLR9, MyD88 and DC-SIGN molecules, but at a lower level than DC(OVA).
1413 17073943 EXO(OVA) can be taken up by DC through LFA-1/CD54 and C-type lectin/mannose (glucosamine)-rich C-type lectin receptor (CLR) interactions.
1414 17073943 Mature DC pulsed with EXO(OVA), which were referred to as mDC(EXO), expressed a higher level of pMHC I, MHC II, and costimulatory CD40, CD54 and CD80 than DC(OVA).
1415 17073943 In this study, we showed that ovalbumin (OVA) protein-pulsed DC (DC(OVA))-derived EXO (EXO(OVA)) displayed MHC class I-OVA I peptide (pMHC I) complexes, CD11c, CD40, CD80, CCR7, DEC205, Toll-like receptor 4 (TLR4), TLR9, MyD88 and DC-SIGN molecules, but at a lower level than DC(OVA).
1416 17073943 EXO(OVA) can be taken up by DC through LFA-1/CD54 and C-type lectin/mannose (glucosamine)-rich C-type lectin receptor (CLR) interactions.
1417 17073943 Mature DC pulsed with EXO(OVA), which were referred to as mDC(EXO), expressed a higher level of pMHC I, MHC II, and costimulatory CD40, CD54 and CD80 than DC(OVA).
1418 17101562 Acute lymphoblastic leukaemia cells express CCR7 but not higher amounts of IL-10 after CD40 ligation.
1419 17108046 Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.
1420 17108046 To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo.
1421 17108046 Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF.
1422 17108046 In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4(+)- and CD8(+)-T-cell responses to SIV Env, compared to standard SIV VLPs.
1423 17108046 We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.
1424 17108046 Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.
1425 17108046 To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo.
1426 17108046 Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF.
1427 17108046 In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4(+)- and CD8(+)-T-cell responses to SIV Env, compared to standard SIV VLPs.
1428 17108046 We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.
1429 17114448 In this study we provide compelling evidence in CD40(-/-) mice demonstrating that IgA CSR can be independent of CD40 signaling and germinal center formation and does not occur in the gut lamina propria (LP) itself.
1430 17114448 The Peyer's patches in CD40(-/-) mice expressed unexpectedly high levels of activation-induced cytidine deaminase mRNA and germline alpha transcripts, but few postswitch circular DNA transcripts, arguing against significant IgA CSR.
1431 17114448 Whereas all of the classical sites for IgA CSR in the GALT in CD40(-/-) mice appeared severely compromised for IgA CSR, B cells in the peritoneal cavity demonstrated the expression of activation-induced cytidine deaminase mRNA comparable to that of wild-type mice.
1432 17114448 In this study we provide compelling evidence in CD40(-/-) mice demonstrating that IgA CSR can be independent of CD40 signaling and germinal center formation and does not occur in the gut lamina propria (LP) itself.
1433 17114448 The Peyer's patches in CD40(-/-) mice expressed unexpectedly high levels of activation-induced cytidine deaminase mRNA and germline alpha transcripts, but few postswitch circular DNA transcripts, arguing against significant IgA CSR.
1434 17114448 Whereas all of the classical sites for IgA CSR in the GALT in CD40(-/-) mice appeared severely compromised for IgA CSR, B cells in the peritoneal cavity demonstrated the expression of activation-induced cytidine deaminase mRNA comparable to that of wild-type mice.
1435 17114448 In this study we provide compelling evidence in CD40(-/-) mice demonstrating that IgA CSR can be independent of CD40 signaling and germinal center formation and does not occur in the gut lamina propria (LP) itself.
1436 17114448 The Peyer's patches in CD40(-/-) mice expressed unexpectedly high levels of activation-induced cytidine deaminase mRNA and germline alpha transcripts, but few postswitch circular DNA transcripts, arguing against significant IgA CSR.
1437 17114448 Whereas all of the classical sites for IgA CSR in the GALT in CD40(-/-) mice appeared severely compromised for IgA CSR, B cells in the peritoneal cavity demonstrated the expression of activation-induced cytidine deaminase mRNA comparable to that of wild-type mice.
1438 17118497 Specifically, the co-culture with activated Vgamma9Vdelta2 T cells with BCG-infected DC resulted in a significant increase of the expression of CD80, CD86, CD40 and CD25 molecules on DC.
1439 17118497 Moreover, DC were able to produce increased levels of TNF-alpha and synthesize ex novo IL-15 without altering the IL-10/IL-12 immunoregulatory pathway.
1440 17118982 Only LT-IIa and LT-IIa(T14S), however, enhanced expression of major histocompatibility complex class II and the costimulatory molecules CD40, CD80, and CD86 on splenic dendritic cells.
1441 17143278 Lipopolysaccharide or CD40 signaling stabilizes Akt1, promoting both activation and Bcl-2-dependent survival of DCs.
1442 17198083 DC pulsed with P. carinii did not demonstrate increased expression of the cell surface markers MHC II, CD40, CD54, CD80 (B7.1), and CD86 (B7.2).
1443 17198083 The release of interleukin (IL)-4 was increased, but there was no increase in the release of interleukin (IL)-12p40, IL-10, tumor necrosis factor-alpha, IL-6, and nitrite compared with naive DC.
1444 17198083 In vivo administration of DC pulsed with P. carinii induced a P. carinii-specific response, generating CD4+ cells that proliferated and released IL-4, but not interferon-gamma, in response to P. carinii-pulsed DC in vitro.
1445 17201654 4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is emerging as an important costimulatory molecule, particularly in the regulation of CD8(+) T cell responses.
1446 17201654 However, 4-1BB is also an important regulator of antiviral CD8(+) T cell responses.
1447 17219364 FACS analysis demonstrated an up-regulation of DC maturation markers CD80, CD86, CD40 and MHC class II upon exposure to Gal-lectin.
1448 17219364 The activation of DC by Gal-lectin was mediated by MAPK and NF-kappaB.
1449 17234309 Murine bone-marrow derived dendritic cells (BMDCs) cultured in the presence of ALVAC secreted high levels of the chemokines CXCL10 and CCL2 and up-regulated expression of the maturation markers CD40, CD80 and CD86.
1450 17235318 Moreover, Ad5:CaPi-treated DCs were activated to express the maturation surface molecules CD40 and CD86, and to secrete proinflammatory cytokines tumor necrosis factor-alpha and interleukin 6.
1451 17235318 Ad5:CaPi also transduced human DC more efficiently than Ad5 alone, similar to a genetically modified vector (Ad5f35) targeted to the CD46 receptor.
1452 17275522 DC were propagated from C3H (H2(k)) bone marrow (BM) using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4).
1453 17275522 Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-beta.
1454 17275522 This observation correlated with reduced interferon-gamma (IFN-gamma) and increased IL-10 production.
1455 17285277 Leukemic cells were stimulated (or not) with CD40L and IL-4.
1456 17285277 Elements of the antigen-processing machinery (MB1, LMP2, LMP7, LMP10, TAP1, TAP2, calnexin, calreticulin, tapasin, ERp57, zeta, delta) were determined by real-time PCR technique.
1457 17285277 The expression of important costimulatory and adhesion molecules considered as DC markers (CD40, CD54, CD80, CD83, CD86) were determined at the mRNA (PCR) and protein (flow cytometry) levels.
1458 17302734 The liposomes did not have an effect on the maturation of murine bone-marrow-derived dendritic cells (BM-DCs) related to the surface expression of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86.
1459 17306360 These should be directed at the level of gene selection and delivery, in order to identify the optimal cytokine and achieve efficient and durable cytokine expression, and at the level of improving immune stimulation, i.e. by co-administration of co-stimulatory molecules including B7 and CD40, or boosting the expression of tumor antigens or MHC class I molecules.
1460 17306360 Interestingly, some of the cytokines which have shown encouraging anti-tumor activity, including IFNs, IL-4, IL-12 and TNF-alpha, are endowed with anti-angiogenic or vasculotoxic effects, which may significantly contribute to local tumor control.
1461 17346201 CD40L substitutes such as CD40-directed agonistic antibodies have been evaluated with interesting results in experimental models.
1462 17371543 The DC phenotype was assessed by CD83 expression, interleukin-12 (IL-12) and IL-10 production, as well as for the ability to polarize T-cell responses.
1463 17371543 Following stimulation with CD40 ligand, DCs matured in the presence of BCG showed enhanced IL-10 and diminished IL-12 production.
1464 17378240 CD40L and IL-4 stimulation of acute lymphoblastic leukemia cells results in upregulation of mRNA level of FLICE--an important component of apoptosis.
1465 17378240 Since it is still unclear whether CD40 ligation drives neoplastic B-cells to apoptosis or not, we assessed the mRNA expression of FLICE, FAS, FADD and TRADD - important components of apoptosis machinery, using real-time PCR in acute lymphoblastic leukemia cells before and after CD40 and IL-4 stimulation.
1466 17378240 ALL cells stimulated with CD40L/IL-4 expressed dendritic cell phenotype at mRNA and protein levels (upregulation of main costimulatory and adhesion molecules noted in real-time RT PCR and flow cytometry); they also expressed higher amounts of mRNA for FLICE, TRADD and FADD after CD40L/IL-4 stimulation.
1467 17378240 However differences statistically significant comparing cells cultured with CD40L/IL-4 and medium alone regarded only FLICE.
1468 17403867 Reduced pathology following infection with transgenic Leishmania major expressing murine CD40 ligand.
1469 17403867 We have previously shown that combining CD40 ligand (CD40L) with Leishmania antigen preferentially induces a type 1 immune response and provides some protection to vaccinated mice (G.
1470 17403867 Reduced pathology following infection with transgenic Leishmania major expressing murine CD40 ligand.
1471 17403867 We have previously shown that combining CD40 ligand (CD40L) with Leishmania antigen preferentially induces a type 1 immune response and provides some protection to vaccinated mice (G.
1472 17425601 Peroxisome proliferator-activated receptor-gamma agonists inhibit respiratory syncytial virus-induced expression of intercellular adhesion molecule-1 in human lung epithelial cells.
1473 17425601 Therefore, we hypothesized whether the detrimental increase of intercellular adhesion molecule-1 (ICAM-1) on RSV-infected lung epithelial cells (A549 and primary normal human bronchial epithelial cells (NHBE)) might be modulated by natural and synthetic PPAR-gamma agonists (15d-PGJ2, ciglitazone, troglitazone, Fmoc-Leu).
1474 17425601 Our data show that all PPAR-gamma agonists under study significantly down-regulated the RSV-induced expression of ICAM-1 on A549- and NHBE cells in a dose-dependent manner resulting in a reduced beta2 integrin-mediated adhesion of monocytic effector cells (U937) to RSV-infected A549 cell monolayers.
1475 17425601 In contrast, the PPAR-alpha agonist bezafibrate had no impact on the RSV-induced ICAM-1 expression.
1476 17425601 The reduced ICAM-1 expression was associated with a diminished ICAM-1 mRNA level and binding activity of nuclear factor-kappaB (p65/p50) in A549 cells.
1477 17484805 In addition, the study demonstrates that PIKA promotes the maturation of bone marrow-derived dendritic cells (BMDCs) including up-regulation of the co-stimulatory molecules CD80, CD86 and CD40, and the induction of cytokines such as IL-12p70, IL-12p40 and IL-6.
1478 17485453 In the absence of CD154, administration of interleukin-12 restores Th1 responses but not protective immunity to Schistosoma mansoni.
1479 17485453 Here we demonstrate the importance of CD40/CD154 in vaccine-induced immunity, as CD154(-/-) mice exposed to RA schistosomes develop no protection to challenge infection.
1480 17485453 We showed that vaccinated CD154(-/-) mice have defective Th1-associated immune responses in the skin-draining lymph nodes and the lungs, with reduced or absent levels of interleukin-12p40 (IL-12p40), gamma interferon, and nitric oxide, but elevated levels of lung IL-4 and IL-5.
1481 17485453 On the other hand, the administration of recombinant IL-12 (rIL-12) to CD154(-/-) mice shortly after vaccination caused elevated and sustained levels of Th1-associated cytokines, rescued MHC-II expression by lung CD11c(+) cells, and restored the appearance of inflammatory effector foci in the lungs.
1482 17532057 Human peripheral blood CD14(+) monocytes were purified by using a magnetic separation column and cultured with GM-CSF and IL-4 to differentiate into immature DCs (iDCs).
1483 17532057 In the presence of Talpha1, iDC surface markers CD40, CD80, MHC class I and class II molecules were significantly upregulated as measured by flow cytemotry analysis.
1484 17532057 Thus, Talpha1 significantly enhances DC differentiation, activation, and functions from human peripheral blood CD14(+) monocytes possibly through a mechanism of the activation of p38 MAPK and NFkappaB pathways.
1485 17548610 Hsp90 inhibition significantly decreased cell surface expression of costimulatory (CD40, CD80, CD86), maturation (CD83), and MHC (HLA-A, B, C and HLA-DP, DQ, DR) markers in immature DC and mature DC and was associated with down-regulation of both RNA and intracellular protein expression.
1486 17553885 Virus-specific CD4 T cells are endowed with multiple functions, such as cytokine production, CD40 ligand (CD40L) expression (associated with the costimulation of CD8 and B cells), and degranulation (associated with cytotoxic potential).
1487 17553885 CD4 T cells specific for each of the viruses produced all seven possible combinations of the cytokines gamma interferon (IFN-gamma), interleukin-2, and tumor necrosis factor alpha.
1488 17590559 Treatment of immature DCs with 7-acyl lipid A and PET lipid A up regulated the surface expression of CD86 and CD40 molecules, and also induced similar profile of pro-inflammatory cytokine secretion.
1489 17626150 Nonspecific CD4(+) T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8(+) CTL responses and long-term T cell memory.
1490 17626150 The active EXO-uptaken CD4(+) T cells (aT(EXO)), expressing acquired exosomal MHC I/OVA I peptide (pMHC I) complexes and costimulatory CD40 and CD80 molecules, can act as APCs capable of stimulating OVA-specific CD8(+) T cell proliferation in vitro and in vivo and inducing efficient CD4(+) Th cell-independent CD8(+) CTL responses in vivo.
1491 17626150 The EXO(OVA)-uptaken CD4(+) aT(EXO) cell vaccine induces much more efficient CD8(+) T cell responses and immunity against challenge of OVA-transfected BL6-10 melanoma cells expressing OVA in wild-type C57BL/6 mice than EXO(OVA).
1492 17626150 The in vivo stimulatory effect of the CD4(+) aT(EXO) cell to CD8(+) T cell responses is mediated and targeted by its CD40 ligand signaling/acquired exosomal CD80 and pMHC I complexes, respectively.
1493 17626150 In addition, CD4(+) aT(EXO) vaccine stimulates a long-term, OVA-specific CD8(+) T cell memory.
1494 17626150 Nonspecific CD4(+) T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8(+) CTL responses and long-term T cell memory.
1495 17626150 The active EXO-uptaken CD4(+) T cells (aT(EXO)), expressing acquired exosomal MHC I/OVA I peptide (pMHC I) complexes and costimulatory CD40 and CD80 molecules, can act as APCs capable of stimulating OVA-specific CD8(+) T cell proliferation in vitro and in vivo and inducing efficient CD4(+) Th cell-independent CD8(+) CTL responses in vivo.
1496 17626150 The EXO(OVA)-uptaken CD4(+) aT(EXO) cell vaccine induces much more efficient CD8(+) T cell responses and immunity against challenge of OVA-transfected BL6-10 melanoma cells expressing OVA in wild-type C57BL/6 mice than EXO(OVA).
1497 17626150 The in vivo stimulatory effect of the CD4(+) aT(EXO) cell to CD8(+) T cell responses is mediated and targeted by its CD40 ligand signaling/acquired exosomal CD80 and pMHC I complexes, respectively.
1498 17626150 In addition, CD4(+) aT(EXO) vaccine stimulates a long-term, OVA-specific CD8(+) T cell memory.
1499 17629370 In contrast, the absence of endogenous IL-12/IL-23 or IL-4 had little impact on the magnitude of the antibody response but instead caused a dramatic change in the pattern of IgG isotypes.
1500 17629370 IFN-gamma was produced by NK, dendritic cells, CD4+ and CD8+ T cells stimulated in vitro with CpG ODN.
1501 17629370 Adoptive transfer experiments confirmed that CD4+ or CD8+ T cells were in fact relevant sources of IFN-gamma in vivo.
1502 17629370 Following CpG ODN injection, splenic dendritic cells from IFN-gamma deficient mice did not up-regulate CD86 or CD40 expression, suggesting a role for these molecules.
1503 17629370 The importance of CD28 (CD86 ligand) was confirmed using CD28 deficient mice which presented severely impaired immune responses following CpG ODN-assisted immunization.
1504 17682046 CD40 ligation has also been shown to trigger autophagic elimination of T. gondii independent of IFN-gamma and p47 GTPases.
1505 17682046 Here we demonstrate that IFN-gamma/p47 GTPase-dependent elimination of T. gondii by strain CPS vaccine-primed macrophages is independent of CD40/tumor necrosis factor signaling.
1506 17682046 Similar to wild-type controls, both CD40-deficient and tumor necrosis factor receptor 1/2 (TNFR1/2)-deficient macrophages can efficiently eliminate invaded strain GFP-PTG and restrain its replication following priming.
1507 17682046 Thus, CD40 and IFN-gamma-induced pathogen elimination might represent two independent resistance pathways, the latter of which plays a primary role in anti-Toxoplasma immunity in mice.
1508 17682046 CD40 ligation has also been shown to trigger autophagic elimination of T. gondii independent of IFN-gamma and p47 GTPases.
1509 17682046 Here we demonstrate that IFN-gamma/p47 GTPase-dependent elimination of T. gondii by strain CPS vaccine-primed macrophages is independent of CD40/tumor necrosis factor signaling.
1510 17682046 Similar to wild-type controls, both CD40-deficient and tumor necrosis factor receptor 1/2 (TNFR1/2)-deficient macrophages can efficiently eliminate invaded strain GFP-PTG and restrain its replication following priming.
1511 17682046 Thus, CD40 and IFN-gamma-induced pathogen elimination might represent two independent resistance pathways, the latter of which plays a primary role in anti-Toxoplasma immunity in mice.
1512 17682046 CD40 ligation has also been shown to trigger autophagic elimination of T. gondii independent of IFN-gamma and p47 GTPases.
1513 17682046 Here we demonstrate that IFN-gamma/p47 GTPase-dependent elimination of T. gondii by strain CPS vaccine-primed macrophages is independent of CD40/tumor necrosis factor signaling.
1514 17682046 Similar to wild-type controls, both CD40-deficient and tumor necrosis factor receptor 1/2 (TNFR1/2)-deficient macrophages can efficiently eliminate invaded strain GFP-PTG and restrain its replication following priming.
1515 17682046 Thus, CD40 and IFN-gamma-induced pathogen elimination might represent two independent resistance pathways, the latter of which plays a primary role in anti-Toxoplasma immunity in mice.
1516 17682046 CD40 ligation has also been shown to trigger autophagic elimination of T. gondii independent of IFN-gamma and p47 GTPases.
1517 17682046 Here we demonstrate that IFN-gamma/p47 GTPase-dependent elimination of T. gondii by strain CPS vaccine-primed macrophages is independent of CD40/tumor necrosis factor signaling.
1518 17682046 Similar to wild-type controls, both CD40-deficient and tumor necrosis factor receptor 1/2 (TNFR1/2)-deficient macrophages can efficiently eliminate invaded strain GFP-PTG and restrain its replication following priming.
1519 17682046 Thus, CD40 and IFN-gamma-induced pathogen elimination might represent two independent resistance pathways, the latter of which plays a primary role in anti-Toxoplasma immunity in mice.
1520 17707139 The same five melanoma epitopes, two co-stimulatory molecules CD80 and CD86, and the CD40 ligand, a marker known to play a crucial role in CTL generation and memory maintenance were encoded in a recombinant Vaccinia virus.
1521 17713013 Intravenous administration of lymphoma cells induced suppression of DC differentiation and maturation assessed as a significant decrease of the IAb, CD80, CD86, CD11b, and CD11c expression on DCs and IAb on splenic APCs.
1522 17713013 Upregulation of APC differentiation was observed in animals after subcutaneous and intraperitoneal administration of lymphoma cells determined as increased expression of CD40 and CD86 in spleen APCs.
1523 17765973 We observed that KLH promotes the activation and maturation of DCs, as assessed by up-regulation of the surface expression of CD80, CD86, CD40, HLA-DR and CD83.
1524 17765973 Moreover, even if KLH stimulated the production of IL-12 and IL-10 by DCs, the final balance was clearly in favour of IL-12.
1525 17850587 Antigen (Ag)-presenting and co-stimulatory capacity of neonatal B-cells was evaluated by staining for major histocompatibility complex (MHC)II, CD80, CD86 and CD40.
1526 17850587 Spleen cells from mice receiving LT-K63 showed enhanced proliferation and interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 secretion upon TT stimulation, whereas cells from mice receiving CpG2006 could only enhance IL-10 secretion.
1527 17916464 These include: (a) pathways to activate professional antigen presenting cells, such as through Toll-like receptors, growth factors, such as GM-CSF, and the CD40 pathway; (b) use of cytokines, such as IL-2, IL-12, and Interferon alpha to enhance immune activation; and (c) pathways that inhibit T cell inhibitory signals, or Tregs.
1528 17920516 These effects are transmitted by a number of cell surface receptors including LRP/CD91, CD40, Toll-like receptors, Scavenger receptors and c-type Lectins.
1529 17942939 We found that mice challenged with MOSEC/luc cells expressing Hsp70 generate significant antigen-specific CD8+ T-cell immune responses.
1530 17942939 In addition, we have shown that CD8+, natural killer, and CD4+ cells are important for protective antitumor effect generated by irradiated tumor cell-based vaccines expressing Hsp70.
1531 17942939 Moreover, we also found that CD40 receptor is most important, followed by Toll-like receptor 4 receptor, for inhibiting in vivo tumor growth of the viable MOSEC/luc expressing Hsp70.
1532 17954761 Lymph node cell populations stimulated with ovalbumin had decreased CD5, CD21, and CD40 expression and increased B-B2, CD25, and CD80 expression on IgM+ cells.
1533 17954761 Stimulation of the same population with purified-protein derivative increased CD25 and CD80 expression on IgM+ cells.
1534 17974997 Enhanced activation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation.
1535 17974997 To enhance DC-based vaccines, we used the combination of a synthetic ligand-inducible CD40 receptor (iCD40) along with Toll-like receptor-4 (TLR-4) ligation in human monocyte-derived DCs.
1536 17974997 The iCD40 receptor permits targeted, reversible activation of CD40 in vivo, potentially bypassing the essential role of CD4(+) T cells for activation of DCs.
1537 17974997 Whereas neither iCD40 nor TLR-4 signaling alone led to high levels of interleukin (IL)-12p70 and IL-6, using iCD40 in combination with lipopolysaccharide (LPS) or monophosphoryl lipid A led to strongly synergistic production of both.
1538 17974997 Enhanced activation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation.
1539 17974997 To enhance DC-based vaccines, we used the combination of a synthetic ligand-inducible CD40 receptor (iCD40) along with Toll-like receptor-4 (TLR-4) ligation in human monocyte-derived DCs.
1540 17974997 The iCD40 receptor permits targeted, reversible activation of CD40 in vivo, potentially bypassing the essential role of CD4(+) T cells for activation of DCs.
1541 17974997 Whereas neither iCD40 nor TLR-4 signaling alone led to high levels of interleukin (IL)-12p70 and IL-6, using iCD40 in combination with lipopolysaccharide (LPS) or monophosphoryl lipid A led to strongly synergistic production of both.
1542 17974997 Enhanced activation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation.
1543 17974997 To enhance DC-based vaccines, we used the combination of a synthetic ligand-inducible CD40 receptor (iCD40) along with Toll-like receptor-4 (TLR-4) ligation in human monocyte-derived DCs.
1544 17974997 The iCD40 receptor permits targeted, reversible activation of CD40 in vivo, potentially bypassing the essential role of CD4(+) T cells for activation of DCs.
1545 17974997 Whereas neither iCD40 nor TLR-4 signaling alone led to high levels of interleukin (IL)-12p70 and IL-6, using iCD40 in combination with lipopolysaccharide (LPS) or monophosphoryl lipid A led to strongly synergistic production of both.
1546 17982663 We used imaging means to demonstrate the conservation of presentation molecules (MHC II, CD1a), co-stimulatory molecules (CD40, CD80, CD86), as well as tumour antigens (Her2/neu, cytokeratins) in optimised conditions.
1547 17991045 We show here that exposure of human DC to live meningococci does not result in a typical maturation response, as determined by the failure to upregulate CD40, CD86, HLA-DR and HLA-Class I.
1548 17991045 Despite this, live meningococci were potent inducers of IL-12 and IL-10, although the ratios of these cytokines differed from those to killed organisms.
1549 18051710 [Linkage of modified human papillomavirus type 16 E7 to CD40 ligand enhances specific CD8+ T-lymphocyte induction and anti-tumour activity of DNA vaccine].
1550 18055209 CD40L disruption enhances Abeta vaccine-mediated reduction of cerebral amyloidosis while minimizing cerebral amyloid angiopathy and inflammation.
1551 18055209 Amyloid-beta (Abeta) immunization efficiently reduces amyloid plaque load and memory impairment in transgenic mouse models of Alzheimer's disease (AD).
1552 18055209 We have shown that blocking the CD40-CD40 ligand (L) interaction mitigates Abeta-induced inflammatory responses and enhances Abeta clearance.
1553 18055209 Further reduction of cerebral amyloidosis in Abeta-immunized PSAPP mice completely deficient for CD40 occurred in the absence of Abeta immunoglobulin G (IgG) antibodies or efflux of Abeta from brain to blood, but was rather correlated with anti-inflammatory cytokine profiles and reduced plasma soluble CD40L.
1554 18079003 Expression of eGFP was augmented in all DC populations upon stimulation with CD40 ligand (CD40L).
1555 18156495 Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production.
1556 18156495 Human monocyte-derived DCs (MoDCs) and the CD1c(+) and CD123(+) peripheral blood DC populations express both activin-A and the type I and II activin receptors.
1557 18156495 Furthermore, MoDCs and CD1c(+) myeloid DCs rapidly secrete high levels of activin-A after exposure to bacteria, specific toll-like receptor (TLR) ligands, or CD40 ligand (CD40L).
1558 18156495 Blocking autocrine activin-A signaling in DCs using its antagonist, follistatin, enhanced DC cytokine (IL-6, IL-10, IL-12p70, and tumor necrosis factor-alpha [TNF-alpha]) and chemokine (IL-8, IP-10, RANTES, and MCP-1) production during CD40L stimulation, but not TLR-4 ligation.
1559 18156495 Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production.
1560 18156495 Human monocyte-derived DCs (MoDCs) and the CD1c(+) and CD123(+) peripheral blood DC populations express both activin-A and the type I and II activin receptors.
1561 18156495 Furthermore, MoDCs and CD1c(+) myeloid DCs rapidly secrete high levels of activin-A after exposure to bacteria, specific toll-like receptor (TLR) ligands, or CD40 ligand (CD40L).
1562 18156495 Blocking autocrine activin-A signaling in DCs using its antagonist, follistatin, enhanced DC cytokine (IL-6, IL-10, IL-12p70, and tumor necrosis factor-alpha [TNF-alpha]) and chemokine (IL-8, IP-10, RANTES, and MCP-1) production during CD40L stimulation, but not TLR-4 ligation.
1563 18184712 We found that protection induced by nonreplicating vaccines requires CD4(+) T cells and CD40/CD40L.
1564 18184828 Positive correlations were found between anti-TBGL immunoglobulin G (IgG) and C-reactive protein (CRP) (r = 0.361; P < 0.001), between anti-TBGL IgA and soluble CD40 ligand (sCD40L) (r = 0.404; P < 0.005), between anti-TBGL IgG and anti-TBGL IgA (r = 0.551; P < 0.0000005), and between anti-TBGL IgM and serum IgM (r = 0.603; P < 0.00000005).
1565 18202224 Here, we report that combinatorial use of CD40 and TLR agonists as a cancer vaccine, compared with monotherapy, elicits high frequencies of self-reactive CD8(+) T cells, potent tumor-specific CD8(+) memory, CD8(+) T cells that efficiently infiltrate the tumor-burdened target organ; therapeutic efficacy; heightened ratios of CD8(+) T cells to FoxP3(+) cells at the tumor site; and reduced hepatotoxicity.
1566 18209042 IFN-gamma itself induced IL-27p28 expression and survival but did not promote relevant CCR7-driven migration or activated Th-1 cell recruitment capacity in MDDC.
1567 18209042 Administered in association with classical maturation stimuli such as CD40 or TLR-4 stimulation, IFN-gamma up-regulated IL-27 and IL-12 production, CCR7-driven migration, and activated Th-1 cell recruitment, whereas it decreased IL-10 production and STAT3 phosphorylation.
1568 18209042 CD38 signaling, which orchestrates migration, survival, and Th-1 polarizing ability of mature MDDC, was involved in IFN-gamma-mediated effects.
1569 18228247 TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation.
1570 18228247 To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation.
1571 18228247 Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals.
1572 18228247 The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos.
1573 18228247 Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity.
1574 18228247 The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos.
1575 18228247 The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity.
1576 18228247 In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells.
1577 18228247 TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation.
1578 18228247 To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation.
1579 18228247 Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals.
1580 18228247 The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos.
1581 18228247 Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity.
1582 18228247 The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos.
1583 18228247 The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity.
1584 18228247 In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells.
1585 18228247 TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation.
1586 18228247 To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation.
1587 18228247 Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals.
1588 18228247 The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos.
1589 18228247 Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity.
1590 18228247 The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos.
1591 18228247 The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity.
1592 18228247 In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells.
1593 18228247 TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation.
1594 18228247 To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation.
1595 18228247 Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals.
1596 18228247 The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos.
1597 18228247 Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity.
1598 18228247 The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos.
1599 18228247 The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity.
1600 18228247 In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells.
1601 18228247 TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation.
1602 18228247 To address this goal, we examined the effects of TLR stimulation on BCR and CD40-induced B cell activation.
1603 18228247 Synergistic production of IL-6 was observed in both human and mouse primary B cells stimulated through B cell antigen receptors, CD40 and TLR7, and these two receptors also cooperated independently of BCR signals.
1604 18228247 The enhanced IL-6 production was dependent upon the activity of c-Jun kinase (JNK) and cFos.
1605 18228247 Dual stimulation through CD40 and TLR7 markedly enhanced JNK activity.
1606 18228247 The increased level of active JNK in dual-stimulated cells was accompanied by an increase in the level of active AP-1 monomers cJun and cFos.
1607 18228247 The stimulation of B cells through both CD40 and TLR7 therefore enhanced the production of cytokines through increased JNK signaling and AP-1 activity.
1608 18228247 In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells.
1609 18311150 In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor signaling pathways, was found to play a crucial part in controlling the maturation, cytokine production and immunostimulatory potency of dendritic cells (DCs).
1610 18311150 A20-silenced DCs showed spontaneous and enhanced expression of costimulatory molecules and proinflammatory cytokines and had different effects on T cell subsets: they inhibited T(reg) cells and hyperactivated tumor-infiltrating cytotoxic T lymphocytes and T helper cells that produced interleukin-6 and tumor necrosis factor-alpha and were refractory to T(reg) cell-mediated suppression.
1611 18354184 Invariant NKT cells promote CD8+ cytotoxic T cell responses by inducing CD70 expression on dendritic cells.
1612 18354184 Using chimeric mice, we now show that the adjuvant properties of iNKT cells require that CD40 triggering and Ag presentation to CD8(+) T cells occur on the same APCs.
1613 18354184 We demonstrate that injection of alpha-galactosylceramide triggers CD70 expression on splenic T cell zone dendritic cells and that this is dependent on CD40 signaling.
1614 18354184 Importantly, we show that blocking the interaction between CD70 and CD27, its costimulatory receptor on T cells, abrogates the ability of iNKT cells to promote a CD8(+) T cell response and abolishes the efficacy of alpha-GalCer as an adjuvant for antitumor vaccines.
1615 18354184 These results define a key role for CD70 in linking the innate response of iNKT cells to the activation of CD8(+) T cells.
1616 18354184 Invariant NKT cells promote CD8+ cytotoxic T cell responses by inducing CD70 expression on dendritic cells.
1617 18354184 Using chimeric mice, we now show that the adjuvant properties of iNKT cells require that CD40 triggering and Ag presentation to CD8(+) T cells occur on the same APCs.
1618 18354184 We demonstrate that injection of alpha-galactosylceramide triggers CD70 expression on splenic T cell zone dendritic cells and that this is dependent on CD40 signaling.
1619 18354184 Importantly, we show that blocking the interaction between CD70 and CD27, its costimulatory receptor on T cells, abrogates the ability of iNKT cells to promote a CD8(+) T cell response and abolishes the efficacy of alpha-GalCer as an adjuvant for antitumor vaccines.
1620 18354184 These results define a key role for CD70 in linking the innate response of iNKT cells to the activation of CD8(+) T cells.
1621 18390718 The amelioration of AIH was directly related to the induction of a specific population of flea antigenic specific T cells exhibiting a CD4(+)CD25(-)FoxP3(+) phenotype, a characteristic of regulatory T (T(REG)) cells.
1622 18390718 These T(REG) cells expressing IL-10, IFN-gamma, and the transcriptional factor T-bet after Ag stimulation were driven by a tolerogenic MHC class II(+)/CD40(low) dendritic cell population that was induced by the coimmunization of DNA and protein vaccines.
1623 18390718 The tolerogenic dendritic cell could educate the naive T cells into CD4(+)CD25(-)FoxP3(+) T(REG) cells both in vitro and in vivo.
1624 18400975 In contrast, their capacity to allostimulate naive CD4(+) T cells resembled that of conventional immature DCs and could be increased by TLR4 stimulation.
1625 18400975 Th1 polarization of CD4(+) T cells and production of interleukin 12p70 (IL-12p70) by ssRNA-DCs were selectively abrogated in response to a late TLR4, but not in response to a CD40, maturation signal.
1626 18400975 Inhibition of p38 mitogen-activated protein kinase partially restored IL-12p70 secretion but did not restore Th1 polarization, whereas addition of exogenous IL-12 led to recovery of Th1 polarization.
1627 18412160 This activated peripheral tissue-derived DC population, characterized by enhanced CD80, CD86, CD40 and IL-12p40 expression, was only identified when focusing on adjuvant- or antigen-labeled CD11c(+) DC, which were found to support T cell proliferation.
1628 18412160 Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen-associated DC but without detectable enhancement of CD80, CD86, CD40 or IL-12p40 expression.
1629 18412160 This activated peripheral tissue-derived DC population, characterized by enhanced CD80, CD86, CD40 and IL-12p40 expression, was only identified when focusing on adjuvant- or antigen-labeled CD11c(+) DC, which were found to support T cell proliferation.
1630 18412160 Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen-associated DC but without detectable enhancement of CD80, CD86, CD40 or IL-12p40 expression.
1631 18413606 The peptide was administered to BALB/c mice three times at monthly intervals, either alone or in the context of a synthetic lipopeptide vaccine candidate (P25-P2C-HPV) produced by linkage of the HPV peptide with a broadly recognized T helper epitope (P25) and the Toll-like receptor-2 (TLR2) ligand dipalmitoyl-S-glyceryl cysteine (P2C).
1632 18413606 The L2-specific antibody response depended on MHC class II, CD40, and MyD88 signaling.
1633 18479787 Therapeutic vaccination with dendritic cells pulsed with tumor-derived Hsp70 and a COX-2 inhibitor induces protective immunity against B16 melanoma.
1634 18479787 Here we sought to overcome this problem by therapeutic vaccination with dendritic cells (DC) pulsed with Hsp70 and a COX-2 inhibitor.
1635 18479787 We found that Hsp70 induces IL-6 and IL-10 production and suppressed expression of CD40 on DC.
1636 18479787 Incubation of DC with tumor-conditioned medium attenuated Hsp70-induced expression of CD80 and induced expression of COX-2.
1637 18479787 Inhibition of COX-2 partially reversed the stimulatory effect of Hsp70 on DC IL-6 and IL-10 production and enhanced expression of CD80 and MHC classes I and II.
1638 18479787 Therapeutic administration of DC pulsed in vitro with Hsp70 in the presence of a COX-2 inhibitor significantly reduced progression of B16 tumors in mice and significantly enhanced survival.
1639 18479787 This was associated with a reduction in the frequency of IL-10-producing CD4(+) T cells and enhancement of IFN-gamma-producing CD8(+) T cells.
1640 18483270 In this study, we have created a chimeric CD40 molecule that incorporates a single chain Fv (scFv) molecule specific for human ErbB2 antigen and fusing to the membrane spanning and cytosolic domains of murine CD40.
1641 18483270 After adenoviral transfer to bone marrow-derived DC, this chimeric receptor (CR) induced nuclear factor-kappaB (NF-kappaB)-dependent DC activation and effector function when cultured with immobilized ErbB2 protein or ErbB2-positive tumor cells in vitro.
1642 18483270 In murine ErbB2-positive D2F2/E2 breast tumor (BALB/c) and EL4/E2 thymoma (C57BL/6) models, i.v. injection of 1 x 10(6) scFv-CD40-DC significantly inhibited tumor growth and cured established tumors.
1643 18523314 Additionally, anti-OVA specific IgE and production of IL-4 and IL-5 of T cells stimulated by OVA were significantly decreased in CD40 siRNA-treated mice.
1644 18562050 A soluble hexameric form of CD40 ligand activates human dendritic cells and augments memory T cell response.
1645 18562050 In addition, the production of soluble functional CD40 ligand has been challenging and the soluble form existing so far is not developed anymore.
1646 18562050 Here, we have evaluated the potency of a new soluble form of hexameric CD40 ligand (sCD40L) to serve as an adjuvant for anti-viral T cell responses. sCD40L was able to activate human DC and to enhance virus-specific memory T cell responses.
1647 18562050 These results demonstrate that this soluble form of CD40 ligand may serve as an adjuvant for T cell response and thus provide the rationale for its potential use in T cell based vaccine strategies.
1648 18562050 A soluble hexameric form of CD40 ligand activates human dendritic cells and augments memory T cell response.
1649 18562050 In addition, the production of soluble functional CD40 ligand has been challenging and the soluble form existing so far is not developed anymore.
1650 18562050 Here, we have evaluated the potency of a new soluble form of hexameric CD40 ligand (sCD40L) to serve as an adjuvant for anti-viral T cell responses. sCD40L was able to activate human DC and to enhance virus-specific memory T cell responses.
1651 18562050 These results demonstrate that this soluble form of CD40 ligand may serve as an adjuvant for T cell response and thus provide the rationale for its potential use in T cell based vaccine strategies.
1652 18562050 A soluble hexameric form of CD40 ligand activates human dendritic cells and augments memory T cell response.
1653 18562050 In addition, the production of soluble functional CD40 ligand has been challenging and the soluble form existing so far is not developed anymore.
1654 18562050 Here, we have evaluated the potency of a new soluble form of hexameric CD40 ligand (sCD40L) to serve as an adjuvant for anti-viral T cell responses. sCD40L was able to activate human DC and to enhance virus-specific memory T cell responses.
1655 18562050 These results demonstrate that this soluble form of CD40 ligand may serve as an adjuvant for T cell response and thus provide the rationale for its potential use in T cell based vaccine strategies.
1656 18562050 A soluble hexameric form of CD40 ligand activates human dendritic cells and augments memory T cell response.
1657 18562050 In addition, the production of soluble functional CD40 ligand has been challenging and the soluble form existing so far is not developed anymore.
1658 18562050 Here, we have evaluated the potency of a new soluble form of hexameric CD40 ligand (sCD40L) to serve as an adjuvant for anti-viral T cell responses. sCD40L was able to activate human DC and to enhance virus-specific memory T cell responses.
1659 18562050 These results demonstrate that this soluble form of CD40 ligand may serve as an adjuvant for T cell response and thus provide the rationale for its potential use in T cell based vaccine strategies.
1660 18562053 CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals.
1661 18562053 CD40 ligand (CD40L), a member of the tumor necrosis factor superfamily (TNFSF), is a pivotal costimulatory molecule for immune responses.
1662 18562053 Co-immunization of mice with CD40L expressing canarypox and the canarypox vaccine expressing HIV-1 proteins, vCP1452, augmented HIV-1 specific cytotoxic T lymphocyte (CTL) responses in terms of frequency, polyfunctionality and interleukin (IL)-7 receptor alpha chain (IL-7Ralpha, CD127) expression.
1663 18562053 In addition, CD40L expressed from canarypox virus could significantly augment CD4+ T cell responses against HIV-1 in mice.
1664 18562053 CD40L expressed from canarypox virus matured human monocyte-derived dendritic cells (MDDCs) in a tumor necrosis factor-alpha (TNF-alpha) independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human individuals and ex vivo HIV-1-specific CTL responses from HIV-1-infected individuals in the presence or absence of CD4+ T cells.
1665 18575270 A number of candidate receptors for Hsp70 on APCs have been proposed to take part in the antitumour immune function including the alpha2 macroglobulin receptor CD91, Toll-like receptors, the signalling receptor CD40 and a number of scavenger receptors.
1666 18600182 Unmodified freeze-thaw tumor cell lysates inhibited the toll-like receptor-induced maturation and function of bone marrow-derived DCs, preventing up-regulation of CD40, CD86, and major histocompatibility complex class II, and reducing secretion of inflammatory cytokines [interleukin (IL)-12 p70, tumor necrosis factor-alpha, and IL-6].
1667 18600182 Although IL-10 secretion was increased by lysate-pulsed DCs, this was not responsible for the observed suppression of IL-12.
1668 18606673 CpG-B was equally effective in stimulating the proliferation of naive B cells of HIV-infected individuals and HIV-negative individuals, and, when combined with BCR and CD40 ligation, cytokine secretion by naive B cells was also comparable in HIV-infected and uninfected individuals.
1669 18628832 Such BVLPs up-regulated the level of CD40, CD80, CD86, CD83, and enhanced the secretion of IL-6, IL-10 and TNF-alpha in immature dendritic cells (DCs).
1670 18628832 BVLPs showed a stronger ability to stimulate DCs in terms of cytokine induction as evidenced by 2 to 6 fold higher production of IL-6 and TNF-alpha.
1671 18628832 Further study indicated that IFN-gamma+ and IL-4+ populations in CD4+ T cells increased upon co-cultivation with DCs pre-exposed with BVLPs or SARS-CoV VLPs.
1672 18632650 Regulatory T cell-resistant CD8+ T cells induced by glucocorticoid-induced tumor necrosis factor receptor signaling.
1673 18632650 We previously found that a Salmonella typhimurium vector engineered to secrete soluble tumor antigen induces CD4(+) T cells resistant to CD4(+)CD25(+) regulatory T cells (Treg) and that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) signal is involved in the development of this resistance.
1674 18632650 In this study, we address the potential of incorporating GITR ligand (GITRL) as a way to augment the immunogenicity of cancer vaccines.
1675 18632650 BALB/c mice were immunized by gene gun with plasmids encoding the mutated extracellular signal-regulated kinase 2 (mERK) with or without plasmids encoding mouse GITRL.
1676 18632650 Coadministration with GITRL during primary and secondary immunization enhanced the induction of mERK-specific CD8(+) T cells.
1677 18632650 Antibody depletion and minigene analysis suggested that GITRL directly activated CTL epitope-specific CD8(+) T cells independently of CD4(+) T cells.
1678 18632650 Immunization with plasmids encoding a CTL epitope and GITRL resulted in strong tumor inhibition in a CD8(+) T cell-dependent manner.
1679 18632650 Furthermore, CTL epitope-specific CD8(+) T cells induced by immunization with plasmids encoding CTL epitope coadministered with GITRL were refractory to suppression by CD4(+)CD25(+) Tregs compared with CD8(+) T cells induced without GITR signaling.
1680 18632650 Regulatory T cell-resistant CD8+ T cells induced by glucocorticoid-induced tumor necrosis factor receptor signaling.
1681 18632650 We previously found that a Salmonella typhimurium vector engineered to secrete soluble tumor antigen induces CD4(+) T cells resistant to CD4(+)CD25(+) regulatory T cells (Treg) and that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) signal is involved in the development of this resistance.
1682 18632650 In this study, we address the potential of incorporating GITR ligand (GITRL) as a way to augment the immunogenicity of cancer vaccines.
1683 18632650 BALB/c mice were immunized by gene gun with plasmids encoding the mutated extracellular signal-regulated kinase 2 (mERK) with or without plasmids encoding mouse GITRL.
1684 18632650 Coadministration with GITRL during primary and secondary immunization enhanced the induction of mERK-specific CD8(+) T cells.
1685 18632650 Antibody depletion and minigene analysis suggested that GITRL directly activated CTL epitope-specific CD8(+) T cells independently of CD4(+) T cells.
1686 18632650 Immunization with plasmids encoding a CTL epitope and GITRL resulted in strong tumor inhibition in a CD8(+) T cell-dependent manner.
1687 18632650 Furthermore, CTL epitope-specific CD8(+) T cells induced by immunization with plasmids encoding CTL epitope coadministered with GITRL were refractory to suppression by CD4(+)CD25(+) Tregs compared with CD8(+) T cells induced without GITR signaling.
1688 18632652 Here, we show that monocyte-derived immature human DCs stimulated with polyinosinic acid:polycytidylic acid, IFN-alpha, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IFN-gamma, alpha-type 1-polarized DC (alpha DC1), secrete profuse amounts of the CXCR3 ligand CXCL9/MIG and substantial amounts of CXCL10/IP-10 and CXCL11/I-TAC after withdrawal of maturation stimuli.
1689 18632652 In sharp contrast, no measurable production of these chemokines was found in DCs after maturation with the current gold standard maturation cocktail for human DC-based cancer vaccines consisting of TNF-alpha, IL-1 beta, IL-6, and prostaglandin-E(2) (PGE(2)-DC).
1690 18632652 PGE(2)-DCs preferentially produced the Th2 and regulatory T-cell-attracting chemokines CCL17/TARC and CCL22/MDC, whereas only marginal levels of these chemokines were produced by alpha DC1s.
1691 18632652 Functional studies in vitro showed that supernatants from mature alpha DC1s actively recruited CD3(-)CD56(+) NK cells and that adding anti-CXCL9/MIG antibodies to the alpha DC1 supernatant substantially reduced this recruitment.
1692 18632652 Finally, alpha DC1s were able to induce IFN-gamma production when cocultured with resting autologous NK cells, but only if concurrent CD40 ligation was provided.
1693 18635004 We demonstrate that an RNA aptamer that recognizes OX40, a member of the tumor necrosis factor receptor superfamily, can be converted into a receptor-activating aptamer by assembling two copies on an olignucleotide-based scaffold.
1694 18708593 DnaK induced the activation of MAPKs and NF-kappaB in DC and the production of the proinflammatory cytokines IL-6, TNF-alpha, and IL-12 p40, as well as low levels of IL-10.
1695 18708593 DnaK induced phenotypic maturation of DC, as demonstrated by an up-regulation of costimulatory molecules CD40, CD80, and CD86.
1696 18708593 DnaK stimulated DC through TLR4 and the adapters MyD88 and Toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) that mediated differential responses.
1697 18708593 DnaK induced activation of MAPKs and NF-kappaB in a MyD88- or TRIF-dependent manner.
1698 18708593 In contrast, DnaK induced DC maturation in a TRIF-dependent, MyD88-independent manner.
1699 18714014 Immunization with two or more TLR agonists, anti-CD40, IFN-gamma, and surfactant were sufficient to drive unprecedented levels of CD8 response to peptide or protein Ag and highly polarized Th1 CD4 responses.
1700 18714014 CD40 signaling was required for CD8 expansion but could be provided by a concomitant CD4 Th response in place of anti-CD40.
1701 18804505 In an experimental model of human monocyte-derived dendritic cells (DCs), the immunophenotype of mature DCs infected with Leishmania donovani and Leishmania major showed a weak decrease in the cell surface expression of CD40, CD86, HLA-DR and DC-SIGN compared with uninfected control DCs.
1702 18813779 In this study, we examine the feasibility of cytokine gene delivery to cancerous lesions in vivo using intravenously administered pathotropically targeted nanoparticles bearing the gene encoding granulocyte/macrophage colony-stimulating factor (GM-CSF; i.e., Reximmune-C).
1703 18813779 In tumor-bearing nude mice, intravenous infusions of Reximmune-C-induced GM-CSF production by transduced cancer cells and paracrine secretion of the cytokine within the tumor nodules, which promoted the recruitment of host mononuclear cells, including CD40+ B cells and CD86+ dendritic cells, into the tumors.
1704 18945879 Downregulation of CD40 ligand response in monocytes from sepsis patients.
1705 18945879 Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed.
1706 18945879 Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules.
1707 18945879 In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production.
1708 18945879 Downregulation of CD40 ligand response in monocytes from sepsis patients.
1709 18945879 Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed.
1710 18945879 Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules.
1711 18945879 In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production.
1712 18977262 Our results provide evidence that poly(I:C12U) is effective in inducing optimal phenotypic (elevated levels of MHC-Class I/Class II, CD83, CCR7, CD86 and CD40 molecules) and functional maturation of human DC in vitro, capable of promoting the production of the inflammatory (Th1-type) cytokine IL-12, with significantly lower levels of IL-10 production, compared to that induced by the parent compound polyI:C.
1713 19013492 TLR4 and MyD88 control protection and pulmonary granulocytic recruitment in a murine intranasal RSV immunization and challenge model.
1714 19013492 An intranasal vaccine composed of Toll-like receptor 2 (TLR2) ligand Neisseria meningitidis outer membrane proteins and Toll-like receptor 4 (TLR4) ligand Shigella flexneri lipopolysaccharide (LPS) (Protollin) and enriched respiratory syncytial virus (RSV) proteins (eRSV) has been demonstrated to promote balanced Th1/Th2 responses without eosinophil recruitment and to protect against challenge in mouse models.
1715 19013492 We used TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) knock-out (-/-) mice to investigate the roles of these signalling pathways on immunogenicity, protection and pulmonary infiltrates following RSV immunization and challenge.
1716 19013492 In contrast, an intact MyD88 pathway was crucial to elicit a balanced type 1:type 2 immune response, characterized by increased splenocyte production of antigen-induced IFNgamma and IL-10 with concomitant reduction of IL5, IgG2a isotype switching and abrogation of pulmonary eosinophil recruitment following challenge.
1717 19013492 Both TLR4 and MyD88-signalling were required for optimal protection against challenge.
1718 19013492 The upregulation of early signalling molecules IFN-beta, TNFalpha, CD40 and CD86 were studied in splenocytes isolated from naïve TLR2, TLR4 and MyD88-/- mice following stimulation with vaccine components.
1719 19013492 Splenocytes from TLR4-/- mice displayed reduced IFN-beta while those of MyD88-/- mice elicited less TNFalpha and lower expression of CD40 and CD86 on CD11c+ cells.
1720 19013492 Together, our results suggest that optimal immunogenicity and protection against RSV without risk of enhanced pulmonary inflammation requires intact TLR4/MyD88-dependent signalling.
1721 19013492 TLR4 and MyD88 control protection and pulmonary granulocytic recruitment in a murine intranasal RSV immunization and challenge model.
1722 19013492 An intranasal vaccine composed of Toll-like receptor 2 (TLR2) ligand Neisseria meningitidis outer membrane proteins and Toll-like receptor 4 (TLR4) ligand Shigella flexneri lipopolysaccharide (LPS) (Protollin) and enriched respiratory syncytial virus (RSV) proteins (eRSV) has been demonstrated to promote balanced Th1/Th2 responses without eosinophil recruitment and to protect against challenge in mouse models.
1723 19013492 We used TLR2, TLR4 and myeloid differentiation factor 88 (MyD88) knock-out (-/-) mice to investigate the roles of these signalling pathways on immunogenicity, protection and pulmonary infiltrates following RSV immunization and challenge.
1724 19013492 In contrast, an intact MyD88 pathway was crucial to elicit a balanced type 1:type 2 immune response, characterized by increased splenocyte production of antigen-induced IFNgamma and IL-10 with concomitant reduction of IL5, IgG2a isotype switching and abrogation of pulmonary eosinophil recruitment following challenge.
1725 19013492 Both TLR4 and MyD88-signalling were required for optimal protection against challenge.
1726 19013492 The upregulation of early signalling molecules IFN-beta, TNFalpha, CD40 and CD86 were studied in splenocytes isolated from naïve TLR2, TLR4 and MyD88-/- mice following stimulation with vaccine components.
1727 19013492 Splenocytes from TLR4-/- mice displayed reduced IFN-beta while those of MyD88-/- mice elicited less TNFalpha and lower expression of CD40 and CD86 on CD11c+ cells.
1728 19013492 Together, our results suggest that optimal immunogenicity and protection against RSV without risk of enhanced pulmonary inflammation requires intact TLR4/MyD88-dependent signalling.
1729 19017930 Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses.
1730 19017930 CD4(+) T cell help is essential for primary CD8(+) T cell responses to noninflammatory Ags.
1731 19017930 IL-2 is one of the principal cytokines made by naive CD4(+) T cells, and we show in this study that it is an essential component of help.
1732 19017930 Adoptively transferred naive CD4(+) TCR-transgenic OT-II cells supported endogenous primary CD8(+) T cell responses, but IL-2-deficient OT-II cells were unable to provide help, although they responded to Ag in vivo and up-regulated CD40 ligand in vitro.
1733 19017930 Wild -type OT-II cells helped endogenous CD8(+) T cell responses in IL-2-deficient mice, but not in IL-2Ralpha-deficient mice.
1734 19017930 Thus, CD4(+) T cell-derived IL-2 is essential for CD8(+) T cell responses to noninflammatory, cell-associated Ags.
1735 19017930 We suggest that it is also a critical component of help for CD8(+) T cell responses to pathogens, because protective memory also requires CD8(+) T cell stimulation by IL-2 during priming.
1736 19020113 We previously reported that LPS-induced de novo expression of RelB is required for generating tolerance to interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) expression.
1737 19020113 RelB represses transcription by binding with heterochromatic protein 1 alpha (HP1alpha) to the proximal promoters of IL-1beta and TNF-alpha.
1738 19020113 In contrast, we report herein that RelB is required for sustained expression of anti-inflammatory IkappaBalpha in LPS-tolerant THP-1 cells.
1739 19020113 RelB transcription activation requires binding to the IkappaBalpha proximal promoter along with NF-kappaB p50 and is associated with an apparent dimer exchange with p65.
1740 19036811 We therefore expressed a viral protein that constitutively activates NF-kappaB, vFLIP from Kaposi's sarcoma-associated herpesvirus (KSHV), in a lentivector to mature DCs. vFLIP activated NF-kappaB in mouse bone marrow-derived DCs in vitro and matured these DCs to a similar extent as lipopolysaccharide; costimulatory markers CD80, CD86, CD40, and ICAM-1 were upregulated and tumor necrosis factor alpha and interleukin-12 secreted.
1741 19036823 Incorporation of CD40 ligand into the envelope of pseudotyped single-cycle Simian immunodeficiency viruses enhances immunogenicity.
1742 19036823 To improve vaccine immunogenicity, we incorporated CD40 ligand (CD40L) into the dSIV envelope.
1743 19036823 Binding of CD40L to its receptor upregulates expression of major histocompatibility complex class I, class II, and costimulatory molecules on DCs and increases production of proinflammatory cytokines and chemokines, especially interleukin 12 (IL-12).
1744 19036823 Expression levels of CD80, CD86, HLA-DR, and CD54 on DCs transduced with the dSIV incorporating CD40L (CD40L-dSIV) were significantly higher than on those transduced with dSIV.
1745 19036823 Moreover, CD40L-dSIV-transduced DCs expressed up to 10-fold more IL-12 than dSIV-transduced DCs.
1746 19036823 Incorporation of CD40 ligand into the envelope of pseudotyped single-cycle Simian immunodeficiency viruses enhances immunogenicity.
1747 19036823 To improve vaccine immunogenicity, we incorporated CD40 ligand (CD40L) into the dSIV envelope.
1748 19036823 Binding of CD40L to its receptor upregulates expression of major histocompatibility complex class I, class II, and costimulatory molecules on DCs and increases production of proinflammatory cytokines and chemokines, especially interleukin 12 (IL-12).
1749 19036823 Expression levels of CD80, CD86, HLA-DR, and CD54 on DCs transduced with the dSIV incorporating CD40L (CD40L-dSIV) were significantly higher than on those transduced with dSIV.
1750 19036823 Moreover, CD40L-dSIV-transduced DCs expressed up to 10-fold more IL-12 than dSIV-transduced DCs.
1751 19049809 In this study, we report a novel direct ex vivo 11-color flow cytometric assay that combines subset identification with analysis of activation status and endocytic ability of three major PBDC subsets (CD1c(+)CD11c(+) "MDC1," CD141(+)CD11c(+) "MDC2," and CD303(+)CD11c(-) "PDC") within a single platform.
1752 19049809 As expected, PBDC identified by this assay express low levels of CD40 and CD86 directly ex vivo, and significantly upregulate expression of these molecules upon stimulation with toll-like receptor ligands LPS and CpG oligonucleotides.
1753 19049809 In addition, PDC internalize FITC-labeled dextran poorly in comparison to MDC1 and MDC2 subsets.
1754 19049809 Furthermore, the combination of surface markers used in this assay reveals a previously unreported CD4(+)CD11c(+)CD303(-)CD1c(-)CD141(-) cell population.
1755 19050242 A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine.
1756 19050242 Polysaccharide (PS)- and protein-specific murine IgG responses to intact Streptococcus pneumoniae (Pn) are both dependent on CD4(+) T cell help, B7-dependent costimulation, and CD40/CD40 ligand interactions.
1757 19050242 We now demonstrate that ICOS(-/-), relative to wild-type, mice elicit a normal PS-specific IgG isotype response to Pn, despite marked inhibition of both the primary and secondary IgG anti-protein (i.e., PspA, PspC, and PsaA) response.
1758 19050242 Finally, although mice that lack the adaptor molecule SAP (SLAM-associated protein) resemble ICOS(-/-) mice (and can exhibit decreased ICOS expression), we observe that the PS-specific, as well as protein-specific, IgG responses to both Pn and conjugate are markedly defective in SAP(-/-) mice.
1759 19050242 These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction.
1760 19066520 The properties of DCs change following stimulation: immature dendritic cells are potent phagocytes, whereas mature DCs are capable of antigen presentation and interaction with CD4+ and CD8+ T cells.
1761 19066520 In this video, we demonstrate flow cytometric comparisons of expression of two co-stimulatory molecules, CD86 and CD40, and the cytokine, IL-12, following overnight stimulation with CpG or mock treatment.
1762 19109450 We measured the activation of the antigen-presenting major histocompatibility complex (MHC) class II molecule, costimulatory molecules CD40 and CD86, the cytokine interleukin-12 (IL-12), and the transcriptional factor interferon regulatory factor 1 (IRF-1) in monocyte-derived macrophages (mMOs) and dendritic cells (mDCs) of adult horses and foals of different ages (from birth to 3 months of age) infected with virulent R. equi or its avirulent, plasmid-cured derivative.
1763 19109450 R. equi infection promoted comparable expression of costimulatory molecules CD86 and CD40 in foal and adult horse cells.
1764 19109450 We measured the activation of the antigen-presenting major histocompatibility complex (MHC) class II molecule, costimulatory molecules CD40 and CD86, the cytokine interleukin-12 (IL-12), and the transcriptional factor interferon regulatory factor 1 (IRF-1) in monocyte-derived macrophages (mMOs) and dendritic cells (mDCs) of adult horses and foals of different ages (from birth to 3 months of age) infected with virulent R. equi or its avirulent, plasmid-cured derivative.
1765 19109450 R. equi infection promoted comparable expression of costimulatory molecules CD86 and CD40 in foal and adult horse cells.
1766 19124765 Typhi(F1) enhanced the activation and maturation of neonatal CD11c+ dendritic cells, shown by increased expression of CD80, CD86, CD40, and MHC-II cell surface markers and production of proinflammatory cytokines IL-12, TNF-alpha, IL-6, and MCP-1.
1767 19124765 Typhi(F1)-stimulated neonatal DC had improved capacity for Ag presentation and T cell stimulation in vitro and induced F1-specific CD4+ and CD8+ T cell responses when adoptively transferred to newborn mice.
1768 19237530 Efficient uptake of the polymeric peptide in vitro resulted in higher expression of the coactivation markers CD80, CD40, and CD70 on dendritic cells and higher proinflammatory cytokine production than with the monomeric peptide.
1769 19240168 Various monoclonal antibodies (mAb) target immune system molecules to enhance immunity by costimulating T cells (i.e., CD137, OX40, CD40, GITR) or interfering in coinhibitory signals (i.e., CTLA-4, PD-1).
1770 19264770 NF-kappaB p50 plays distinct roles in the establishment and control of murine gammaherpesvirus 68 latency.
1771 19264770 Because the confounding impact of the loss of p50 on the host response to MHV68 infection prevented a direct analysis of the role of this NF-kappaB family member on MHV68 latency in B cells, we generated and infected mixed p50(+/+)/p50(-/-) bone marrow chimeric mice.
1772 19264770 NF-kappaB p50 plays distinct roles in the establishment and control of murine gammaherpesvirus 68 latency.
1773 19264770 Because the confounding impact of the loss of p50 on the host response to MHV68 infection prevented a direct analysis of the role of this NF-kappaB family member on MHV68 latency in B cells, we generated and infected mixed p50(+/+)/p50(-/-) bone marrow chimeric mice.
1774 19380779 LPS is a natural adjuvant that potentiates Ag-specific T cell survival and Th1 differentiation by stimulating MyD88 and Toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) signaling pathways.
1775 19380779 Most of the T cells primed in TRIF-deficient mice failed to up-regulate CXCR3 and had an overall reduced capacity to produce IFN-gamma, demonstrating effector T cell differentiation was linked to their migration.
1776 19380779 Although TNF neutralization reduced T cell numbers, its coneutralization with IL-10 unexpectedly restored the T cells, suggesting the balance between pro- and anti-inflammatory cytokines influences T cell survival rather than their magnitude.
1777 19380779 Boosting with a CD40 agonist in addition to LPS restored the effector CD8 T cell response in livers of TRIF-deficient mice while only partially restoring CD4 T cells, suggesting that LPS primes CD8 and CD4 T cell immunity through different mechanisms.
1778 19399172 Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC cross-linking antibody modulates T cell functions.
1779 19399172 One such phenotype, the B7-DC XAb-induced antigen accumulation in mTLR-matured DCs, has been linked to signaling through TREM-2, but the signals required for other DC phenotypes critical for the therapeutic effects in animal models remain unclear.
1780 19399172 Here, FRET and co-immunoprecipitation studies show that CD40 is recruited to the multi-molecular complex by B7-DC XAb.
1781 19399172 Signals emanating from CD40 are important, as CD40(-/-) DCs treated with B7-DC XAb (DC(XAb)) activated DAP12, but failed to activate NFkappaB, and were not protected from cell death upon cytokine withdrawal or treatment with Vitamin D(3).
1782 19399172 CD40(-/-) DC(XAb) also failed to secrete IL-6 and were unable to support the conversion of T regulatory cells into IL-17+ effector T cells in vitro.
1783 19399172 Importantly, the expression of CD40 was required for the overall ability of B7-DC XAb to induce anti-tumor CTL, to provide protection from a number of tumor types, and for DC(XAb) to be effective anti-tumor vaccines in vivo.
1784 19399172 Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC cross-linking antibody modulates T cell functions.
1785 19399172 One such phenotype, the B7-DC XAb-induced antigen accumulation in mTLR-matured DCs, has been linked to signaling through TREM-2, but the signals required for other DC phenotypes critical for the therapeutic effects in animal models remain unclear.
1786 19399172 Here, FRET and co-immunoprecipitation studies show that CD40 is recruited to the multi-molecular complex by B7-DC XAb.
1787 19399172 Signals emanating from CD40 are important, as CD40(-/-) DCs treated with B7-DC XAb (DC(XAb)) activated DAP12, but failed to activate NFkappaB, and were not protected from cell death upon cytokine withdrawal or treatment with Vitamin D(3).
1788 19399172 CD40(-/-) DC(XAb) also failed to secrete IL-6 and were unable to support the conversion of T regulatory cells into IL-17+ effector T cells in vitro.
1789 19399172 Importantly, the expression of CD40 was required for the overall ability of B7-DC XAb to induce anti-tumor CTL, to provide protection from a number of tumor types, and for DC(XAb) to be effective anti-tumor vaccines in vivo.
1790 19399172 Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC cross-linking antibody modulates T cell functions.
1791 19399172 One such phenotype, the B7-DC XAb-induced antigen accumulation in mTLR-matured DCs, has been linked to signaling through TREM-2, but the signals required for other DC phenotypes critical for the therapeutic effects in animal models remain unclear.
1792 19399172 Here, FRET and co-immunoprecipitation studies show that CD40 is recruited to the multi-molecular complex by B7-DC XAb.
1793 19399172 Signals emanating from CD40 are important, as CD40(-/-) DCs treated with B7-DC XAb (DC(XAb)) activated DAP12, but failed to activate NFkappaB, and were not protected from cell death upon cytokine withdrawal or treatment with Vitamin D(3).
1794 19399172 CD40(-/-) DC(XAb) also failed to secrete IL-6 and were unable to support the conversion of T regulatory cells into IL-17+ effector T cells in vitro.
1795 19399172 Importantly, the expression of CD40 was required for the overall ability of B7-DC XAb to induce anti-tumor CTL, to provide protection from a number of tumor types, and for DC(XAb) to be effective anti-tumor vaccines in vivo.
1796 19399172 Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC cross-linking antibody modulates T cell functions.
1797 19399172 One such phenotype, the B7-DC XAb-induced antigen accumulation in mTLR-matured DCs, has been linked to signaling through TREM-2, but the signals required for other DC phenotypes critical for the therapeutic effects in animal models remain unclear.
1798 19399172 Here, FRET and co-immunoprecipitation studies show that CD40 is recruited to the multi-molecular complex by B7-DC XAb.
1799 19399172 Signals emanating from CD40 are important, as CD40(-/-) DCs treated with B7-DC XAb (DC(XAb)) activated DAP12, but failed to activate NFkappaB, and were not protected from cell death upon cytokine withdrawal or treatment with Vitamin D(3).
1800 19399172 CD40(-/-) DC(XAb) also failed to secrete IL-6 and were unable to support the conversion of T regulatory cells into IL-17+ effector T cells in vitro.
1801 19399172 Importantly, the expression of CD40 was required for the overall ability of B7-DC XAb to induce anti-tumor CTL, to provide protection from a number of tumor types, and for DC(XAb) to be effective anti-tumor vaccines in vivo.
1802 19399172 Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC cross-linking antibody modulates T cell functions.
1803 19399172 One such phenotype, the B7-DC XAb-induced antigen accumulation in mTLR-matured DCs, has been linked to signaling through TREM-2, but the signals required for other DC phenotypes critical for the therapeutic effects in animal models remain unclear.
1804 19399172 Here, FRET and co-immunoprecipitation studies show that CD40 is recruited to the multi-molecular complex by B7-DC XAb.
1805 19399172 Signals emanating from CD40 are important, as CD40(-/-) DCs treated with B7-DC XAb (DC(XAb)) activated DAP12, but failed to activate NFkappaB, and were not protected from cell death upon cytokine withdrawal or treatment with Vitamin D(3).
1806 19399172 CD40(-/-) DC(XAb) also failed to secrete IL-6 and were unable to support the conversion of T regulatory cells into IL-17+ effector T cells in vitro.
1807 19399172 Importantly, the expression of CD40 was required for the overall ability of B7-DC XAb to induce anti-tumor CTL, to provide protection from a number of tumor types, and for DC(XAb) to be effective anti-tumor vaccines in vivo.
1808 19444444 Upon infection or vaccination, CD40L is typically increased on the surface of CD4 helper T cells during activation, and this increased expression is absolutely essential to the CD40L promotion of expansion of antigen-specific B cells and CD 8 effector T cells in response to infection or vaccination [Singh et al.
1809 19444444 In aged human beings and mice, the reduced levels of expression of CD40 ligand (CD40L) in activated CD4 helper T cells is dramatically reduced [Eaton et al.
1810 19498460 Numerous studies have shown that treatment of mice with an agonistic mAb, clone DTA-1, targeting murine glucocorticoid-induced tumor necrosis factor receptor (GITR) results in enhanced immune responses in tumor-bearing animals.
1811 19498460 To illustrate the broad utility of this strategy, we show that DC transfected with mRNA encoding GITR-ligand/Fc fusion protein is also an effective tumor vaccine adjuvant.
1812 19524453 The role of CD40 and CD154/CD40L in dendritic cells.
1813 19532135 We further found that the increased numbers of mature CD45RA(+)CD8alpha(+)CD40(+) pDCs infiltrated into Ad-BD2-E1A-treated tumors.
1814 19539498 It is well recognized that activation of CD40 on antigen presenting cells by its ligand, CD154, expressed on T-lymphocytes, contributes to the pro-inflammatory response necessary for eradication of infection, yet pathological in autoimmunity.
1815 19539498 While the exact role of CD40 on CD8 T cells remains controversial, it does appear to contribute to the adaptive immune response against infection.
1816 19539498 CD40 on CD4 T cells, on the other hand, plays a functional role in the autoimmune disease process.
1817 19539498 It is well recognized that activation of CD40 on antigen presenting cells by its ligand, CD154, expressed on T-lymphocytes, contributes to the pro-inflammatory response necessary for eradication of infection, yet pathological in autoimmunity.
1818 19539498 While the exact role of CD40 on CD8 T cells remains controversial, it does appear to contribute to the adaptive immune response against infection.
1819 19539498 CD40 on CD4 T cells, on the other hand, plays a functional role in the autoimmune disease process.
1820 19539498 It is well recognized that activation of CD40 on antigen presenting cells by its ligand, CD154, expressed on T-lymphocytes, contributes to the pro-inflammatory response necessary for eradication of infection, yet pathological in autoimmunity.
1821 19539498 While the exact role of CD40 on CD8 T cells remains controversial, it does appear to contribute to the adaptive immune response against infection.
1822 19539498 CD40 on CD4 T cells, on the other hand, plays a functional role in the autoimmune disease process.
1823 19539989 To assess the immune response, cell surface markers including MHC II, CD86, CD40, and CD209 and cytokines including IL-6, IL-12p40, and IL-10 were measured.
1824 19540594 Requirement of TLR4 and CD14 in dendritic cell activation by Hemagglutinin B from Porphyromonas gingivalis.
1825 19540594 Using an endotoxin free rHagB preparation, our results show that stimulation of murine bone marrow-derived DC with rHagB leads to upregulation of the costimulatory molecules CD86 and CD40, activation of p38 and ERK MAP kinases, transcription factors NF-kappaB, CREB and IRF-3 and the production of IL-6, TNF-alpha, IL-12p40 and to a lesser extent IL-10 and IFN-beta.
1826 19540594 This activation process was absolutely dependent on TLR4 and CD14.
1827 19540594 While upregulation of CD86 was independent of the adaptor molecule MyD88, CD40 upregulation and optimal cytokine (IL-6, TNF-alpha, IL-12p40, IL-10 and IFN-beta) production required both MyD88 and TRIF molecules.
1828 19540594 Requirement of TLR4 and CD14 in dendritic cell activation by Hemagglutinin B from Porphyromonas gingivalis.
1829 19540594 Using an endotoxin free rHagB preparation, our results show that stimulation of murine bone marrow-derived DC with rHagB leads to upregulation of the costimulatory molecules CD86 and CD40, activation of p38 and ERK MAP kinases, transcription factors NF-kappaB, CREB and IRF-3 and the production of IL-6, TNF-alpha, IL-12p40 and to a lesser extent IL-10 and IFN-beta.
1830 19540594 This activation process was absolutely dependent on TLR4 and CD14.
1831 19540594 While upregulation of CD86 was independent of the adaptor molecule MyD88, CD40 upregulation and optimal cytokine (IL-6, TNF-alpha, IL-12p40, IL-10 and IFN-beta) production required both MyD88 and TRIF molecules.
1832 19578865 We investigated the effect of different toll like receptor (TLR) agonists including LPS (TLR4 agonist), polyinosinic acid-polycytidylic acid (PIC, TLR3 agonist), CpG oligonucleotide (TLR9 agonist), and imiquimod (TLR7 agonist) on human monocyte-derived dendritic cells (mdDCs) loading of human papillomavirus (HPV) type 11 E7 epitope.
1833 19578865 This was characterized by an enhanced expression of CD40, CD80, CD86, CD83 and HLA-DR, and a high level of IL-12 production.
1834 19580785 Human monocyte-derived immature or LPS- and cytokine-matured DCs were exposed to ambient or 40 mmHg increased pressure for 12h, then assessed for expression of CD80, CD86, CD40, MHC-I/II, and inflammatory cytokine production.
1835 19609245 Generation of human dendritic cells that simultaneously secrete IL-12 and have migratory capacity by adenoviral gene transfer of hCD40L in combination with IFN-gamma.
1836 19609245 In this study, we exploit an adenoviral vector encoding human CD40 ligand (CD40L), Ad5hCD40L, to establish DCs that feature both migration potential and prolonged secretion of the key T-helper 1 cytokine interleukin-12p70 (IL-12p70).
1837 19609245 Finally, DCs transduced with both Ad5hCD40L and an adenoviral vector encoding the melanoma antigen MelanA/MART-1 and treated with MC and IFN-gamma efficiently primed naive autologous CD8+ T cells into antigen-specific cytotoxic T lymphocyte.
1838 19609245 This strategy to generate DCs that exert both migration capacity and prolonged IL-12p70 secretion after intracellular CD40L expression and IFN-gamma treatment has the potential to further improve current DC vaccination protocols.
1839 19632790 CD40 ligand (CD40L) is the major signal that induces B cells to efficiently present antigen to T cells, and CD40-activated B (CD40-B) lymphocyte cells may boost cytotoxic T lymphocytes (CTLs) when they are pulsed with tumour antigens.
1840 19641529 Here, we show that B-cells activated through the toll-like receptor-9 (TLR-9) and CD40 up-regulate surface expression of major histocompatibility complex and costimulatory molecules, produce IL-12, and exhibit potent antigen-presenting properties in vitro.
1841 19725226 RNA electroporated CD40 ligand-activated B cells can induce cytotoxic T-lymphocyte response in vitro.
1842 19725226 C57BL/6 mouse spleen B cells were activated by anti-mouse CD40 antibody, recombinant interleukin-4, and cyclosporin A, and then electroporated with total RNA from Hepal-6 cells (Hepal-6 RNA-CD40mAb-B cells).
1843 19725226 RNA electroporated CD40 ligand-activated B cells can induce cytotoxic T-lymphocyte response in vitro.
1844 19725226 C57BL/6 mouse spleen B cells were activated by anti-mouse CD40 antibody, recombinant interleukin-4, and cyclosporin A, and then electroporated with total RNA from Hepal-6 cells (Hepal-6 RNA-CD40mAb-B cells).
1845 19742349 [Cellular immunity induced by CD40 ligand-activated dendritic cells in CEA transgenic mice].
1846 19801508 CD40- or TLR7-stimulated B cell APCs induced similar CD8(+) T cell responses, but costimulation through the BCR and TLR7 produced a more effective Bvac as measured by T cell stimulation and the protection of mice from an infectious pathogen.
1847 19853910 The effect of R1, R2 and R3 on the expression of the pro- and anti-inflammatory cytokines (TNF-alpha, IL-6, and IL-12) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) in MDDCs was examined.
1848 19853910 The exposure of R1 caused a dose-dependent increase in the expression of TNF-alpha, IL-12, CD86 and CD40, while R2 and R3 did not up-regulate these cytokines and co-stimulatory molecules.
1849 19853910 Furthermore, we found that R1 significantly increased the NF-kappaB expression in the nucleus (in a dose-dependent manner) and promoted the degradation of total IkappaBalpha levels, indicating that the NF-kappaB signaling pathway might involve in an R1-induced DC activation.
1850 19853910 The effect of R1, R2 and R3 on the expression of the pro- and anti-inflammatory cytokines (TNF-alpha, IL-6, and IL-12) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) in MDDCs was examined.
1851 19853910 The exposure of R1 caused a dose-dependent increase in the expression of TNF-alpha, IL-12, CD86 and CD40, while R2 and R3 did not up-regulate these cytokines and co-stimulatory molecules.
1852 19853910 Furthermore, we found that R1 significantly increased the NF-kappaB expression in the nucleus (in a dose-dependent manner) and promoted the degradation of total IkappaBalpha levels, indicating that the NF-kappaB signaling pathway might involve in an R1-induced DC activation.
1853 20002303 The DC population was expanded in BALB/C mice (H-2(d) ) by hydrodynamic injection of a plasmid pUMVC3-hFLex expressing the secreted portion of the human Fms-like tyrosine kinase receptor-3 ligand (hFlt3).
1854 20002303 Cellular immune responses were determined with respect to secretion of INFγ and IL2 by CD4(+) cells and cytotoxic T-lymphocyte (CTL) assays in vitro; inhibition of tumour cell growth was employed for the assessment of CD8(+) generated activity in vivo.
1855 20002303 We found that Flt3L treatment expanded the DC population in the spleen to 43%, and such cells displayed a striking upregulation of CD86 as well as CD80 and CD40 co-stimulating molecules.
1856 20022123 This FcgammaR ligation induced a significantly enhanced expression of Major Histocompatibility complex (MHCII) class II and the costimulatory molecules CD80/86 and CD40 by MoDC compared with immature MoDC.
1857 20022123 The F4-IC induced DC maturation correlated with significant higher expression levels of several pro-inflammatory cytokines such as interleukine (IL) 1beta, IL-6 and Tumor necrosis factor alpha, the chemokine IL-8 and IL-12p40 in comparison with immature MoDC.
1858 20071492 Two components, C16:0-LPC and C18:0-LPC, were identified to be capable of the upregulation of expression of CD86, HLA-DR, and CD40 on in vitro-cultured monocyte-derived DCs from healthy donors.
1859 20071492 Both induced the release of chemokines to high concentrations (macrophage inflammatory protein 1, monocyte chemoattractant protein 1) or moderate concentrations (interleukin-8 [IL-8], gamma interferon-inducible protein 10).
1860 20071492 The intravenous injection of C16:0-LPC or C18:0-LPC into mice resulted in the detectable secretion of IL-6 and IL-5 in sera.
1861 20072155 Selective elimination of a chemoresistant side population of B-CLL cells by cytotoxic T lymphocytes in subjects receiving an autologous hCD40L/IL-2 tumor vaccine.
1862 20072155 To discover whether drug-resistant malignant SP cells are nonetheless sensitive to immune-mediated killing, we first established the presence of a malignant CD5(+)CD19(+) SP subset in the blood of 18/21 subjects with B-cell chronic lymphocytic leukemia (B-CLL).
1863 20072155 We examined the fate of these cells in six of these individuals who received autologous human CD40 ligand and interleukin-2 (hCD40L/IL-2) gene-modified tumor cells as part of a tumor vaccine study.
1864 20072155 Vaccinated patients showed an increase in B-CLL-reactive T cells followed by a corresponding decline in circulating CD5(+)CD19(+) SP cells.
1865 20072155 Elimination of SP cells is likely triggered by their increased expression of target antigens, such as receptor for hyaluronan-mediated motility (RHAMM), after stimulation of the malignant cells by hCD40L, as CD8(+) RHAMM-specific T cells could be detected in the peripheral blood of immunized patients and were associated with the decline in B-CLL SP cells.
1866 20079918 Exacerbation of corneal scarring in HSV-1 gK-immunized mice correlates with elevation of CD8+CD25+ T cells in corneas of ocularly infected mice.
1867 20079918 Infiltration of the cornea by CD4+, CD8+, CD25+, CD4+CD25+, CD8+CD25+, CD19+, CD40+, CD40L+, CD62L+, CD95+, B7-1+, B7-2+, MHC-I+, and MHC-II+ cells was monitored by immunohistochemistry, qRT-PCR and FACS at various times post-infection (PI).
1868 20079918 This study demonstrated for the first time that the presence of CD8+CD25+ T cells in the cornea is correlated with exacerbation of CS in the gK-immunized group.
1869 20087927 There was a synergistic increase in cytokine production (TNF-alpha, IL-6, IL-10, and IFN-beta) in BM-DCs, together with an increase in the expression of co-stimulatory molecules (CD86 and CD40) in response to co-treatment with poly(I:C) and zymosan.
1870 20087927 The results of the current study suggest that one of the mechanisms by which zymosan enhances the adjuvant activity of poly(I:C) is through increased cytokine production by DCs involving the synergistic activation of poly(I:C)-induced TLR3- and zymosan-induced TLR2-mediated signaling pathways.
1871 20121696 Two families of receptors, the CD28 family and the tumor necrosis factor receptor (TNFR) family, have been found to be major players in providing costimulation to CD8+ T cells.
1872 20121696 Programmed death-1 (PD-1), another member of the CD28 family, may contribute to functional defects of helpless memory CD8+ T cells.
1873 20121696 Members of the TNFR family, such as CD27, 4-1BB, CD40, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and OX40, have also been implicated in the survival, generation, maintenance, and quality of virus-specific memory CD8+T cells.
1874 20121696 The delivery of costimulatory molecules such as CD28, 4-1BB, and OX40 can help boost the generation and function of virus-specific memory CD8+ T cells.
1875 20121696 Two families of receptors, the CD28 family and the tumor necrosis factor receptor (TNFR) family, have been found to be major players in providing costimulation to CD8+ T cells.
1876 20121696 Programmed death-1 (PD-1), another member of the CD28 family, may contribute to functional defects of helpless memory CD8+ T cells.
1877 20121696 Members of the TNFR family, such as CD27, 4-1BB, CD40, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and OX40, have also been implicated in the survival, generation, maintenance, and quality of virus-specific memory CD8+T cells.
1878 20121696 The delivery of costimulatory molecules such as CD28, 4-1BB, and OX40 can help boost the generation and function of virus-specific memory CD8+ T cells.
1879 20160099 To improve the efficacy of T cell-based vaccination, we pursued the principle that CD4(+) T cells provide help for functional CD8(+) T cell immunity.
1880 20160099 To achieve strong CD4(+) T cell immunity, the protein vaccine was targeted selectively to DEC-205, a receptor for antigen presentation on dendritic cells.
1881 20160099 CD4(+) helper cells upon adoptive transfer allowed wild-type, but not CD40(-/-), recipient mice to respond better to the DNA vaccine.
1882 20200275 Activation of tolerogenic dendritic cells in the tumor draining lymph nodes by CD8+ T cells engineered to express CD40 ligand.
1883 20200275 In this study, we investigated the effects of local delivery of CD40L by tumor-reactive CD8(+) T cells on dendritic cell activation and antitumor T cell responses in the TRAMP model.
1884 20200275 To increase the immunostimulatory signal, CD40L was engineered, by deleting the majority of the cytoplasmic domain, to increase its levels of expression and duration on the surface of CD8(+) T cells.
1885 20200275 Tumor-reactive CD8(+) T cells expressing the truncated form of CD40L stimulated maturation of dendritic cells in vitro and in the prostate draining lymph nodes in vivo.
1886 20200275 Following dendritic cell maturation, a significantly higher fraction of adoptively transferred, tumor-reactive (reporter) CD8(+) T cells was stimulated to express IFN-gamma and infiltrate the prostate tissue.
1887 20200275 The antitumor CD8(+) T cell response was further enhanced if TRAMP mice were also immunized with a tumor-specific Ag.
1888 20205645 This phenomenon is associated with increased expression of membrane-bound CD40 with its cognate ligand, CD40 ligand (CD40L), as well as increased circulating levels of soluble forms of CD40 (sCD40) and CD40L (sCD40L).
1889 20207993 By contrast, the Peyer's patch (PP) was the dominant IgA CSR site in both CD40(-/-) and wild type (WT) mice, and they both hosted similar levels of mRNA expression for B cell activating factor of the TNF family, a proliferation inducing ligand, and inducible NO synthase, potential switch-factors for IgA.
1890 20207993 These findings reconcile that IgA CSR can occur in PP in the absence of GC with the fact that CD40(-/-) mice host near normal levels of IgA plasma cells in the LP.
1891 20207993 By contrast, the Peyer's patch (PP) was the dominant IgA CSR site in both CD40(-/-) and wild type (WT) mice, and they both hosted similar levels of mRNA expression for B cell activating factor of the TNF family, a proliferation inducing ligand, and inducible NO synthase, potential switch-factors for IgA.
1892 20207993 These findings reconcile that IgA CSR can occur in PP in the absence of GC with the fact that CD40(-/-) mice host near normal levels of IgA plasma cells in the LP.
1893 20306041 These cells induced differentiation of DC into semi-mature antigen-presenting cells expressing CD86, CD11c, CD54, HLA-DR, CD83 and CD40, which secreted low levels of bioactive IL-12 but no IL-10.
1894 20306041 When substituted for Vgamma9Vdelta2 T cells, IFN-gamma did not induce full DC maturation but it augmented IL-12 and inhibited IL-10 release by LPS-stimulated DC, in a manner similar to HMB-PP-activated Vgamma9Vdelta2 T cells.
1895 20332049 Expression of co-stimulatory molecules (CD40, CD80, CD86, and MHC-II) and cytokines (IL-12p40, TNF-alpha, and IFN-gamma) was increased in BMDC treated with LT-IIa-B(5).
1896 20382498 CD40/CD40L signaling, one of the most important co-stimulatory molecules is capable of effectively skewing the immune response by promoting DCs maturation and co-stimulation.
1897 20387165 Here, immature DCs are electroporated with mRNAs encoding a tumor antigen, CD40 ligand (CD40L), CD70, and constitutively active (caTLR4) to generate mature antigen-presenting DCs.
1898 20417300 In this paper, we studied the immunostimulatory activity of the recombinant BCG strains in vitro and found out that rBCG-A(N)-E-A(C) activated THP-1 cells and induced higher expression levels of CD86, CD80, CD40 and HLA-DR, especially increased the ratio of CD86/CD80.
1899 20417300 Moreover, rBCG-A(N)-E-A(C) up-regulated the expression of EFHD2, ACTB and ACTG1 in the macrophages and improved the ability of antigen presentation and the CD8(+) T-cells immune response.
1900 20435931 Knockdown of CD40, CD80, and CD86, prior to loading DCs with the arthritogenic Ag collagen II, led to a population of cells that could effectively suppress onset of collagen-induced arthritis.
1901 20435931 Disease suppression was associated with inhibition of collagen II-specific Ab production and suppression of T cell recall responses.
1902 20435931 Downregulation of IL-2, IFN-gamma, TNF-alpha, and IL-17 and increased FoxP3(+) cells with regulatory activity were observed in collagen-induced arthritis mice treated with siRNA-transfected DCs.
1903 20457264 Polychromatic flow cytometry was used to examine CD4(+) T cells for levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and CD154 (CD40 ligand) expression after stimulation with inactivated flu virus.
1904 20457264 CD4(+) T cell expression of CD154 and cytokine responses were significantly reduced in HCT recipients compared to healthy adults.
1905 20457264 A lack of B cell reconstitution and dysfunctional CD4 T cell costimulation (as marked by low CD154 expression) is associated with low NAb levels postvaccination in HCT patients.
1906 20471443 Incorporation of CD40 ligand into SHIV virus-like particles (VLP) enhances SHIV-VLP-induced dendritic cell activation and boosts immune responses against HIV.
1907 20471443 Engagement of CD40 with CD40L induces dendritic cell (DC) maturation and activation, thereby promoting immune responses.
1908 20471443 We found that CD83, CD40, and CD86 were significantly up-regulated and significantly increased cytokines production were observed after hCD40L/SHIV-VLP treatment in human CD14(+) monocyte-derived DCs as compared to SHIV-VLP treatment.
1909 20471443 Mice immunized with mCD40L/SHIV-VLP showed more than a two-fold increase in HIV Env-specific IgG antibody production, an increase in SIV Gag and HIV Env-specific IFN-gamma and IL-4 producing cells, and an increase in HIV Env-specific cytotoxic activity compared to that in SHIV-VLP immunized mice.
1910 20471443 Furthermore, multifunctional CD4(+) Th1 cells, which simultaneously produce IFN-gamma, IL-2 and TNF-alpha triple cytokines, and CD8(+) T-cells, which produce IFN-gamma were elevated in the mCD40L/SHIV-VLP immunized group.
1911 20471443 Therefore, incorporation of CD40L into VLP may represent a novel strategy to develop effective HIV vaccines.
1912 20471443 Incorporation of CD40 ligand into SHIV virus-like particles (VLP) enhances SHIV-VLP-induced dendritic cell activation and boosts immune responses against HIV.
1913 20471443 Engagement of CD40 with CD40L induces dendritic cell (DC) maturation and activation, thereby promoting immune responses.
1914 20471443 We found that CD83, CD40, and CD86 were significantly up-regulated and significantly increased cytokines production were observed after hCD40L/SHIV-VLP treatment in human CD14(+) monocyte-derived DCs as compared to SHIV-VLP treatment.
1915 20471443 Mice immunized with mCD40L/SHIV-VLP showed more than a two-fold increase in HIV Env-specific IgG antibody production, an increase in SIV Gag and HIV Env-specific IFN-gamma and IL-4 producing cells, and an increase in HIV Env-specific cytotoxic activity compared to that in SHIV-VLP immunized mice.
1916 20471443 Furthermore, multifunctional CD4(+) Th1 cells, which simultaneously produce IFN-gamma, IL-2 and TNF-alpha triple cytokines, and CD8(+) T-cells, which produce IFN-gamma were elevated in the mCD40L/SHIV-VLP immunized group.
1917 20471443 Therefore, incorporation of CD40L into VLP may represent a novel strategy to develop effective HIV vaccines.
1918 20471443 Incorporation of CD40 ligand into SHIV virus-like particles (VLP) enhances SHIV-VLP-induced dendritic cell activation and boosts immune responses against HIV.
1919 20471443 Engagement of CD40 with CD40L induces dendritic cell (DC) maturation and activation, thereby promoting immune responses.
1920 20471443 We found that CD83, CD40, and CD86 were significantly up-regulated and significantly increased cytokines production were observed after hCD40L/SHIV-VLP treatment in human CD14(+) monocyte-derived DCs as compared to SHIV-VLP treatment.
1921 20471443 Mice immunized with mCD40L/SHIV-VLP showed more than a two-fold increase in HIV Env-specific IgG antibody production, an increase in SIV Gag and HIV Env-specific IFN-gamma and IL-4 producing cells, and an increase in HIV Env-specific cytotoxic activity compared to that in SHIV-VLP immunized mice.
1922 20471443 Furthermore, multifunctional CD4(+) Th1 cells, which simultaneously produce IFN-gamma, IL-2 and TNF-alpha triple cytokines, and CD8(+) T-cells, which produce IFN-gamma were elevated in the mCD40L/SHIV-VLP immunized group.
1923 20471443 Therefore, incorporation of CD40L into VLP may represent a novel strategy to develop effective HIV vaccines.
1924 20502628 The 40K-OMP-specific CD4(+) T cells induced by oral 40K-OMP plus CpG ODN produced both Th1 (IFN-gamma) and Th2 (IL-4) cytokines.
1925 20502628 Furthermore, increased frequencies of CD11c(+)B220(+) DCs and CD11c(+)CD11b(+) DCs with up-regulated expression of CD80, CD86, CD40 and MHC II molecules were noted in spleen, Peyer's patches and cervical lymph nodes.
1926 20525895 The release of IFN-gamma and IL-12, the signature cytokines of Th1 responses, was enhanced by V-Oka but blocked by virulent VZV.
1927 20525895 V-Oka and virulent VZV efficiently synergized with CD40L, eliminating the possibility that CD40 signaling was a target of VZV-associated immune evasion.
1928 20532647 Animals exhibited a relatively normal CD4/CD8 ratio (average 1.63:1) as well as reconstitution of CD3/CD56 (averaging 17.8%) and CD20 subsets (averaging 4.0%).
1929 20532647 Animals reconstituted with donor-matched CD11c+ DC also demonstrated a CD11c+ population within their spleen, representing 0.27% to 0.43% of the recovered human cells with concurrent expression of HLA-DR, CD40, and CD86.
1930 20551839 Use of anti-CTLA4 and anti-PD1 antibodies, realization of the importance of co-stimulatory signals, which translated into the use of agonist CD40 monoclonal antibodies, as well as activation of innate immunity through enhanced expression of co-stimulatory molecules on the surface of dendritic cells by TLR agonists are only a few items on the list of recent advances in the treatment of melanoma.
1931 20618329 Optimizing dendritic cell-based immunotherapy in multiple myeloma: intranodal injections of idiotype-pulsed CD40 ligand-matured vaccines led to induction of type-1 and cytotoxic T-cell immune responses in patients.
1932 20618329 To improve the efficacy of DC vaccination in myeloma, we investigated the use of Id- and keyhole limpet haemocyanin (KLH)-pulsed, CD40 ligand-matured DCs administered intranodally.
1933 20618329 In summary, intranodal administration of Id-pulsed CD40 ligand-matured DCs was able to induce Id-specific T and B-cell responses in patients.
1934 20618329 Optimizing dendritic cell-based immunotherapy in multiple myeloma: intranodal injections of idiotype-pulsed CD40 ligand-matured vaccines led to induction of type-1 and cytotoxic T-cell immune responses in patients.
1935 20618329 To improve the efficacy of DC vaccination in myeloma, we investigated the use of Id- and keyhole limpet haemocyanin (KLH)-pulsed, CD40 ligand-matured DCs administered intranodally.
1936 20618329 In summary, intranodal administration of Id-pulsed CD40 ligand-matured DCs was able to induce Id-specific T and B-cell responses in patients.
1937 20618329 Optimizing dendritic cell-based immunotherapy in multiple myeloma: intranodal injections of idiotype-pulsed CD40 ligand-matured vaccines led to induction of type-1 and cytotoxic T-cell immune responses in patients.
1938 20618329 To improve the efficacy of DC vaccination in myeloma, we investigated the use of Id- and keyhole limpet haemocyanin (KLH)-pulsed, CD40 ligand-matured DCs administered intranodally.
1939 20618329 In summary, intranodal administration of Id-pulsed CD40 ligand-matured DCs was able to induce Id-specific T and B-cell responses in patients.
1940 20851084 CD40 ligand expressed in adenovirus can improve the immunogenicity of the GP3 and GP5 of porcine reproductive and respiratory syndrome virus in swine.
1941 20851084 In this study, the recombinant adenoviruses expressing porcine CD40 ligand (CD40L) and GP3/GP5 of PRRSV were constructed and the immune responses were examined in pigs.
1942 20851084 CD40 ligand expressed in adenovirus can improve the immunogenicity of the GP3 and GP5 of porcine reproductive and respiratory syndrome virus in swine.
1943 20851084 In this study, the recombinant adenoviruses expressing porcine CD40 ligand (CD40L) and GP3/GP5 of PRRSV were constructed and the immune responses were examined in pigs.
1944 20876821 It is thought that use of formalin deconforms viral epitopes of RSV, resulting in poor Toll-like receptor (TLR) stimulation; suboptimal maturation of dendritic cells with reduced production of activation factors CD40, CD80, and CD86; decreased germinal center formation in lymph nodes; and the production of nonprotective antibodies.
1945 21051091 We prepared mature allogeneic dendritic cells from bone marrow and then assessed their phenotype (CD80, CD83, CD86, CD1a, CD11c, CD40 and MHC II), antigen uptake and presenting abilities.
1946 21093495 Our results showed that the infection of bmDCs with SA14-14-2 resulted in viral replication and upregulation of bmDC maturation marker molecules (CD40, CD80, CD83 and MHC I).
1947 21093495 SA14-14-2 infection also stimulated the production of interferon-α (IFN-α), monocyte chemoattractant protein-1 (MCP-1/CCL2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) of bmDC.
1948 21115722 Nasal immunization with a fusion protein consisting of the hemagglutinin A antigenic region and the maltose-binding protein elicits CD11c(+) CD8(+) dendritic cells for induced long-term protective immunity.
1949 21115722 Analysis of cytokine responses showed that nasal administration of 25k-hagA-MBP induced antigen-specific CD4(+) T cells producing interleukin 4 (IL-4) and IL-5, but not gamma interferon (IFN-γ), in the spleen and cervical lymph nodes (CLNs).
1950 21115722 Furthermore, increased numbers of CD11c(+) CD8α(+), but not CD11c(+) CD11b(+) or CD11c(+) B220(+), dendritic cells with upregulated expression of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) molecules were noted in the spleen, CLNs, and nasopharynx-associated lymphoreticular tissues (NALT).
1951 21150714 Here, we show that interferon-γ is a key cytokine conditioning the dendritic cell to induce the expression of CD40, CD80, CD86, and CD54 on Dex, endowing them with direct and potent peptide-dependent CD8(+) T-cell-triggering potential in vitro and in vivo.
1952 21177916 Internalization of IgG-coated targets results in activation and secretion of soluble CD40 ligand and RANTES by human platelets.
1953 21177916 To this end, we observed that interaction with IgG-coated beads resulted in platelet activation (as measured by CD62P expression), internalization of targets, and significant soluble CD40 ligand (sCD40L) and RANTES (regulated upon activation, normal T cell expresses and secreted) secretion.
1954 21177916 Internalization of IgG-coated targets results in activation and secretion of soluble CD40 ligand and RANTES by human platelets.
1955 21177916 To this end, we observed that interaction with IgG-coated beads resulted in platelet activation (as measured by CD62P expression), internalization of targets, and significant soluble CD40 ligand (sCD40L) and RANTES (regulated upon activation, normal T cell expresses and secreted) secretion.
1956 21177920 Here, we investigated the protein levels of nuclear transcription factor NF-κB (p50, p65, and p105), IκBα (inhibitor of NF-κB), T-cell receptor (TCR) CD3ζ-chain, tyrosine kinase p56(LCK), and nuclear factor of activated T cells c2 (NF-ATc2) in peripheral blood CD4(+) T cells from patients with sarcoidosis.
1957 21177920 The reduced levels of p65 in sarcoid CD4(+) T cells concurred with decreased levels of p50, p105, CD3ζ, p56(LCK), IκBα, and NF-ATc2.
1958 21177920 Polyclonal stimulation of NF-κB-deficient sarcoid T cells resulted in reduced expression of CD69 and CD154, decreased proliferation, and cytokine (i.e., interleukin 2 [IL-2] and gamma interferon [IFN-γ]) production.
1959 21239998 CD40L was expressed on the surface of virus-like particles (VLPs) to target HIV-1 Gag antigens to the CD40 receptor on DCs, whereas CD40L-CD40 interaction would also result in cellular activation.
1960 21239998 Multiple CD40L VLP constructs were made and evaluated in vitro and in vivo.
1961 21240487 Various studies have shown that positive costimulatory pathways such as the CD28 and CD40 pathways can influence the expansion and cytokine production by iNKT cells.
1962 21240487 To study whether PD-L1 deficiency on NKT cells would enhance antigen-specific T-cell responses, we utilized CD8(+) OT-1 OVA transgenic T cells. α-GalCer enhanced the expansion and cytokine production of OT-1 CD8(+) cells after adoptive transfer into wild-type recipients.
1963 21240487 However, this expansion was significantly enhanced when OT-1 CD8(+) T cells were adoptively transferred into PD-L1(-/-) recipients.
1964 21240487 PD-L1(-/-) mice given dendritic cells loaded with antigen and α-GalCer had a significant reduction in tumor growth and this was associated with increased trafficking of antigen-presenting cells and CD8(+) T cells to the tumors.
1965 21240487 These data demonstrate that abrogating PDL1:PD-1 interactions during the activation of iNKT cells amplifies an anti-tumor response when coupled with DC vaccination.
1966 21328541 The SapM mutant BCG vaccine was more effective than the parental vaccine in inducing recruitment and activation of CD11c(+) MHC-II(int) CD40(int) dendritic cells (DCs) to the draining lymph nodes.
1967 21368092 HBHA induced DC maturation in a TLR4-dependent manner, elevating expression of the surface molecules CD40, CD80, and CD86, MHC classes I and II and the proinflammatory cytokines IL-6, IL-12, IL-1β, TNF-α, and CCR7, as well as stimulating the migratory capacity of DCs in vitro and in vivo.
1968 21368092 Mechanistic investigations established that MyD88 and TRIF signaling pathways downstream of TLR4 mediated secretion of HBHA-induced proinflammatory cytokines.
1969 21368092 HBHA-treated DCs activated naïve T cells, polarized CD4(+) and CD8(+) T cells to secrete IFN-γ, and induced T-cell-mediated cytotoxicity.
1970 21374321 It now appears that various types of immunomodulatory molecules such as cytokines (IL-1 [1], IL-2 [2], IL-12 [3], IFN-γ [4], IL-7 [5-7], and GM-CSF [8,9]), chemokines (TCA-3 [10], RANTES [11], MIP-1 [11]), and costimulatory molecules (CD40L [12], B7-1 [13] and B7-2 [14]) could enhance or modify the specific immune responses elicited by DNA immunization (see Table 1).
1971 21374321 Cytokine proteins IL-1 Antibody (Ab) ↑ (23,24) IL-2 Ab ↑ (2,25,26) IL-12 TH1(DTH) ↑ (3) IFN-γ Ab, DTH ↑ (4,25,27) GM-CSF Ab ↑ (28,29) B.
1972 21374321 Expression plasmids IL-12 CTL ↑(i.m. and i.n.) (15,21,22,30) DTH ↑(i.m. and i.n.) (5,21) Ab →(i.m. and i.n.) (15,22) GM-CSF Ab ↑(i.m.) (9,18,22 CTL ↑(i.m.) (18) (3)H-TdR uptake ↑(i.m.) (9) TCA3 CTL ↑(i.m.) (31) DTH ↑(i.m.) (31) Ab →(i.m.) (31) B7-1 CTL →(i.m.) (19) DTH →(i.m.) (19) Ab →(i.m.) (19) B7-2 CTL ↑(i.m.) (19) DTH ↑(i.m.) (19) Ab →(i.m.) (19) CD40(L) Ab →(i.m.)
1973 21382487 PBMC were stimulated polyclonally using CD40 Ligand, IL-21 and CpG to induce B cell proliferation and differentiation into antibody secreting cells (ASCs).
1974 21383499 A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy.
1975 21383499 Here, we have engineered a drug-inducible, composite activation receptor for DCs (referred to herein as DC-CAR) comprising the TLR adaptor MyD88, the CD40 cytoplasmic region, and 2 ligand-binding FKBP12 domains.
1976 21383499 AP1903-activated iMyD88/CD40-transduced human or mouse DCs also produced higher levels of Th1 cytokines, showed improved migration in vivo, and enhanced both antigen-specific CD8+ T cell responses and innate NK cell responses.
1977 21383499 A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy.
1978 21383499 Here, we have engineered a drug-inducible, composite activation receptor for DCs (referred to herein as DC-CAR) comprising the TLR adaptor MyD88, the CD40 cytoplasmic region, and 2 ligand-binding FKBP12 domains.
1979 21383499 AP1903-activated iMyD88/CD40-transduced human or mouse DCs also produced higher levels of Th1 cytokines, showed improved migration in vivo, and enhanced both antigen-specific CD8+ T cell responses and innate NK cell responses.
1980 21383499 A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy.
1981 21383499 Here, we have engineered a drug-inducible, composite activation receptor for DCs (referred to herein as DC-CAR) comprising the TLR adaptor MyD88, the CD40 cytoplasmic region, and 2 ligand-binding FKBP12 domains.
1982 21383499 AP1903-activated iMyD88/CD40-transduced human or mouse DCs also produced higher levels of Th1 cytokines, showed improved migration in vivo, and enhanced both antigen-specific CD8+ T cell responses and innate NK cell responses.
1983 21389871 The resulting DCs showed strongly-enhanced IL-12p70 production on subsequent T-cell interaction compared with immature DCs (average of 19-fold enhancement) and nonpolarized IL-1β/TNF-α/IL-6/PGE(2)-matured "standard" DCs (average of 215-fold enhancement).
1984 21389871 Additional inclusion of polyinosinic: polycytidylic acid during NK-DC cocultures optimized the expression of CD80, CD86, CD40, and HLA-DR on the resulting (NK)DC1, increased their CCR7-mediated migratory responsiveness to the lymph node-associated chemokine CCL21, and further enhanced their IL-12-producing capacity.
1985 21400024 Here, we use three target epitopes, two derived from tumor antigens [Mart1(26-34) (M26) and Cyp1B1(239-247) (Cyp239)] and one derived from the influenza A viral antigen [FluM1(58-66) (FluM58)], to demonstrate that CD40-activated B cells, like dendritic cells, have a limited capability to process certain tumor antigens.
1986 21463625 DCs were generated from peripheral blood monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
1987 21463625 Compared to DCs treated with E7 in a 2-D culture model, the expression of co-stimulatory molecules CD80 and CD40 were significantly increased in the 3-D model (p<0.05), and a remarkable increase of IL-12 p70 was observed.
1988 21499439 The expression of CD1a, CD38, CD40, CD54, CD80, CD83, CD86, HLA-DR and CCR7 on URC-primed DC was enhanced.
1989 21499439 The production of IL-12p70 by URC-primed DC was inhibited by the anti-Toll-like receptor 4 (TLR4) monoclonal antibody (mAb), but partially abolished by anti-TLR2 mAb. mRNA coding for TLR2 and TLR4 was expressed in URC-primed DC.
1990 21499439 DC matured with URC had an intermediate migratory capacity towards CCL19 and CCL21.
1991 21538408 CpG 684 was proved biologically active, capable of up-regulating the expressions of CD40 and CD86 molecules.
1992 21538408 CpG 684 at 150 µg per rat led to decreases in peripheral lymphocyte, serum globulin, glucose, alkaline phosphatase and K+ levels in female rats, and induced the decrease in serum albumin and total protein in rats of both sexes.
1993 21538973 Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells.
1994 21538973 We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also stimulate cell maturation, leading to more potent immune responses.
1995 21538973 We have shown that a recombinant, monomeric CD40 ligand fusion protein conjugated to polystyrene micro- and nanoparticles led to significantly enhanced uptake by DCs in vitro.
1996 21538973 The uptake appeared to be specifically mediated by CD40L binding to CD40 expressed on DCs.
1997 21538973 These findings suggest that CD40 ligand may be a potentially useful targeting moiety for delivery of particulate vaccines to DCs, and that further optimization of both CD40L and the polymer carriers is necessary to achieve efficacy in vivo.
1998 21538973 Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells.
1999 21538973 We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also stimulate cell maturation, leading to more potent immune responses.
2000 21538973 We have shown that a recombinant, monomeric CD40 ligand fusion protein conjugated to polystyrene micro- and nanoparticles led to significantly enhanced uptake by DCs in vitro.
2001 21538973 The uptake appeared to be specifically mediated by CD40L binding to CD40 expressed on DCs.
2002 21538973 These findings suggest that CD40 ligand may be a potentially useful targeting moiety for delivery of particulate vaccines to DCs, and that further optimization of both CD40L and the polymer carriers is necessary to achieve efficacy in vivo.
2003 21538973 Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells.
2004 21538973 We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also stimulate cell maturation, leading to more potent immune responses.
2005 21538973 We have shown that a recombinant, monomeric CD40 ligand fusion protein conjugated to polystyrene micro- and nanoparticles led to significantly enhanced uptake by DCs in vitro.
2006 21538973 The uptake appeared to be specifically mediated by CD40L binding to CD40 expressed on DCs.
2007 21538973 These findings suggest that CD40 ligand may be a potentially useful targeting moiety for delivery of particulate vaccines to DCs, and that further optimization of both CD40L and the polymer carriers is necessary to achieve efficacy in vivo.
2008 21538973 Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells.
2009 21538973 We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also stimulate cell maturation, leading to more potent immune responses.
2010 21538973 We have shown that a recombinant, monomeric CD40 ligand fusion protein conjugated to polystyrene micro- and nanoparticles led to significantly enhanced uptake by DCs in vitro.
2011 21538973 The uptake appeared to be specifically mediated by CD40L binding to CD40 expressed on DCs.
2012 21538973 These findings suggest that CD40 ligand may be a potentially useful targeting moiety for delivery of particulate vaccines to DCs, and that further optimization of both CD40L and the polymer carriers is necessary to achieve efficacy in vivo.
2013 21538973 Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells.
2014 21538973 We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also stimulate cell maturation, leading to more potent immune responses.
2015 21538973 We have shown that a recombinant, monomeric CD40 ligand fusion protein conjugated to polystyrene micro- and nanoparticles led to significantly enhanced uptake by DCs in vitro.
2016 21538973 The uptake appeared to be specifically mediated by CD40L binding to CD40 expressed on DCs.
2017 21538973 These findings suggest that CD40 ligand may be a potentially useful targeting moiety for delivery of particulate vaccines to DCs, and that further optimization of both CD40L and the polymer carriers is necessary to achieve efficacy in vivo.
2018 21577140 The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC).
2019 21577140 This pilot clinical trial evaluated the feasibility, safety, and immunogenicity of a therapeutic vaccination containing autologous TriMix-DC co-electroporated with mRNA encoding a human leukocyte antigen class II-targeting signal linked to 1 of 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, and gp100) in patients with advanced melanoma.
2020 21633673 Our results demonstrated up to an approximately fivefold induction in the infiltration of CD3(+) cells in tumor mass on STAT3 knockdown with high levels of CD4(+), CD8(+), and NKT cells.
2021 21633673 Those DCs were activated, in an otherwise suppressive microenvironment, as evidenced by a high expression of costimulatory molecules CD86 and CD40.
2022 21674065 We report an alternative approach, independent of BCR, for stimulating resting B (RB) cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity.
2023 21722668 In the present work we demonstrated that recombinant human calcineurin subunit B (rhCnB) stimulated the expression of the surface molecules CD83, CD80, CD86, CD40, and HLA-DR.
2024 21722668 It also promoted secretion of inflammatory cytokines IL-6, TNF-α, and IL-1β by human PBMC-derived dendritic cells.
2025 21722668 Transcript levels of cytokines such as IL-4, IL-10, and IFN-γ in the splenocytes were also upregulated when in vitro stimulated with pneumolysin.
2026 21742437 CD40 and CD154 interaction is critically important in regulating humoral and cell-mediated immune responses.
2027 21746857 A Salmonella vector vaccine expressing the saliva-binding region (SBR) of the adhesin AgI/II of Streptococcus mutans has been shown to induce a mixed Th1/Th2 anti-SBR immune response in mice and to require Toll-like receptor 2 (TLR2), TLR4, and MyD88 signaling for the induction of mucosal anti-SBR antibody responses.
2028 21746857 Bone marrow-derived DC from wild-type and TLR2, TLR4, and MyD88 knockout mice were stimulated with Salmonella vector BRD509, the SBR-expressing Salmonella vector vaccine BRD509(pSBRT7), or SBR protein, and the DC responses to different stimuli were compared by assessing costimulatory molecule expression, cytokine production, and signaling pathways.
2029 21746857 BRD509(pSBRT7) and BRD509 induced upregulation of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) expression.
2030 21746857 The low IL-12p40 and high IL-6 cytokine profile expressed by BRD509(pSBRT7)-stimulated DC may represent a shift toward a Th2 response, as suggested by the increased expression in Jagged-1.
2031 21746859 CD40 ligand (CD40L) transduction of antigen-pulsed dendritic cells (DCs) can result in antigen-specific humoral immune responses even in CD4(+) T-cell-depleted settings.
2032 21746859 Here, we show that CD40L transduction of DCs results in the induction of interleukin-12p40 (IL-12p40), IL-12p70, and IL-23.
2033 21746859 Antigen-specific recall responses in CD4-deficient mice were critically dependent on IL-12p40 and IL-23p19 expression in DCs and were not affected by the lack of IL-12p35.
2034 21746859 To confirm that this defect in recall was due to IL-23, transduction of IL-12p40(-/-) DCs with a recombinant adenovirus expressing functional IL-23 restored recall responses in DC-vaccinated CD4-deficient mice.
2035 21746859 These data show that DC-produced IL-23 is critical for vaccine-induced antigen-specific IgG2c and recall antibody responses in the setting of CD4(+) T-cell depletion.
2036 21747119 DC activation also requires interaction of CD40 with its ligand CD40L to generate protective T-cell-mediated tumor immunity.
2037 21747119 Furthermore, CD40 targeting improved the induction of specific CD8(+) T cells along with therapeutic efficacy in a mouse model of melanoma.
2038 21747119 DC activation also requires interaction of CD40 with its ligand CD40L to generate protective T-cell-mediated tumor immunity.
2039 21747119 Furthermore, CD40 targeting improved the induction of specific CD8(+) T cells along with therapeutic efficacy in a mouse model of melanoma.
2040 21799517 In c-Cbl-deficient dendritic cells, Toll-like receptor-induced expression of proinflammatory factors, such as interleukin-12, is increased, correlating with a greater potency of dendritic-cell-based vaccines against established tumours.
2041 21799517 In addition, c-Cbl deficiency reduces both p50 and p105 levels, which have been shown to modulate the stimulatory function of NF-κB.
2042 21882825 Coculture of functionalized nanoparticles with bone marrow-derived DCs significantly increased cell surface expression of MHC II, the T cell costimulatory molecules CD86 and CD40, the C-type lectin receptor CIRE and the mannose receptor CD206 over the nonfunctionalized nanoparticles.
2043 21882825 Blocking the mannose and CIRE receptors prior to the addition of functionalized nanoparticles to the culture inhibited the increased surface expression of MHC II, CD40 and CD86.
2044 21882825 Coculture of functionalized nanoparticles with bone marrow-derived DCs significantly increased cell surface expression of MHC II, the T cell costimulatory molecules CD86 and CD40, the C-type lectin receptor CIRE and the mannose receptor CD206 over the nonfunctionalized nanoparticles.
2045 21882825 Blocking the mannose and CIRE receptors prior to the addition of functionalized nanoparticles to the culture inhibited the increased surface expression of MHC II, CD40 and CD86.
2046 21914064 The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning.
2047 21914064 Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4(IL-4).
2048 21914064 We find that, compared with control groups, modification of DCs with HBV S-ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA-DR) and proinflammatory cytokines (IL-12).
2049 21934655 Identification of molecular adjuvants to in vivo "modulate " DC to coordinately render improved Th1 and CD8 T cell immunity, and attenuated deleterious Treg effects, is a critical challenge.
2050 21934655 This immunization strategy is based on a genetic vaccine encoding both cytomegalovirus (CMV)-driven vaccine Aghsp70 and DC-specific CD11c-driven XBP1s.
2051 21934655 The novel targeted vaccine induced durable Th1 and CD8 T cell responses to poorly immunogenic self/tumor antigen (Ag) and attenuated tumor-associated Treg suppressive function.
2052 21934655 Bone marrow (BM)-derived DC genetically modified to simultaneously overexpress XBP1s and express Aghsp70 upregulated CD40, CD70, CD86, interleukin (IL)-15, IL-15Rα, and CCR7 expression, and increased IL-6, IL-12, and tumor necrosis factor (TNF)-α production in vitro.
2053 21983157 The activation markers MHC-class-II, CD40, CD80 and CD86 on DCs were significantly upregulated by BCG-CS as compared to wild-type BCG (wt-BCG).
2054 21994357 Interestingly, we show that upon activation by anti-CD40 and gamma interferon (IFN-γ), B cells from PKR(-/-) mice show diminished major histocompatibility complex class II (MHC II), CD80, and CD86 levels on the cell surface compared to wild-type (WT) mice.
2055 21994357 Our data also show that PKR is necessary for optimal expression of adhesion molecules, such as CD11a and ICAM-1, that are necessary for homotypic aggregation of B cells.
2056 21994357 Furthermore, in this report we demonstrate for the first time that upon CD40 ligation, PKR is rapidly phosphorylated and activated, indicating that PKR is an early and novel downstream mediator of CD40 signaling pathways.
2057 22002164 Immunization was greatly improved by targeting HIV gag p24 to DCs with an antibody to DEC-205, a DC receptor for antigen uptake and processing.
2058 22002164 Within 4 h, GLA caused DCs to upregulate CD86 and CD40 and produce cytokines including IL-12p70 in vivo.
2059 22015603 Our results demonstrated that treatment with the improved DC vaccine which was tumor cell lysate pulsed with M2 and OK (HMO-D), compared with H-D and HM-D, significantly increased cell surface markers (MHC-I and II, CD40, CD80, CD86 and CD11c) expression on DCs, enhanced Th1-type cytokines (IL-12, TNF-α and IFN-γ) production but not Th2-type cytokine (IL-5) production, induced remarkable high levels of lymphocytes proliferation and CD8(+) cytotoxic T-lymphocyte (CTL).
2060 22194898 DCs were evaluated for antigen uptake, and following maturation with LPS and IFN-gamma, DCs were assessed for expression of CD80, CD40, CD86, ICAM-1 and CCR7, production of IL-12p70 and IP-10, and induction of tumor-specific T-cell responses.
2061 22194898 Mature Day-7 DCs expressed the highest CD40 and ICAM-1, but mature Day-4 DCs produced the most IL-12p70 and IP-10.
2062 22194898 DCs were evaluated for antigen uptake, and following maturation with LPS and IFN-gamma, DCs were assessed for expression of CD80, CD40, CD86, ICAM-1 and CCR7, production of IL-12p70 and IP-10, and induction of tumor-specific T-cell responses.
2063 22194898 Mature Day-7 DCs expressed the highest CD40 and ICAM-1, but mature Day-4 DCs produced the most IL-12p70 and IP-10.
2064 22233931 CD40/APC-specific antibodies with three T-cell epitopes loaded in the constant domains induce CD4+ T-cell responses.
2065 22233931 Targeting of antigen to antigen presenting cells (APCs) increases peptide loading of major histocompatibility complex (MHC) class II molecules and CD4+ T-cell activation.
2066 22266281 OX40 ligand and programmed cell death 1 ligand 2 expression on inflammatory dendritic cells regulates CD4 T cell cytokine production in the lung during viral disease.
2067 22266281 Using a mouse model in which vaccination with vaccinia virus vectors expressing the respiratory syncytial virus (RSV) fusion protein (rVVF) or attachment protein (rVVG) leads to type 1- or type 2-biased cytokine responses, respectively, upon RSV challenge, we found expression of CD40 and OX40 ligand (OX40L) on lung inflammatory DCs was higher in rVVF-primed mice than in rVVG-primed mice early after RSV challenge, whereas the reverse was observed later in the response.
2068 22266281 In contrast, PD-L2 promoted IFN-γ production, irrespective of conditions, suppressing IL-5 only if expressed on type 1-biased DCs.
2069 22323527 Here, we report an approach to arm an oncolytic virus with CD40 ligand (CD40L) to stimulate beneficial immunologic responses in patients.
2070 22323527 In contrast, high levels of virus, CD40L, and RANTES were documented locally at the tumor.
2071 22349523 CD40 ligand enhances immunogenicity of vector-based vaccines in immunocompetent and CD4+ T cell deficient individuals.
2072 22349523 CD40 ligand (CD40L or CD154), a member of the tumor necrosis factor superfamily (TNFSF), is an important co-stimulatory molecule and, through interactions with its cognate receptor CD40, plays a pivotal role in the generation of host immune responses.
2073 22349523 Exploitation of CD40L and its receptor CD40 could provide a means to enhance and potentially restore protective immune responses in CD4+ T cell deficiency.
2074 22349523 Co-immunization of mice with CD40L and Ag85B by intranasal or intramuscular prime-boosting led to route-dependent enhancement of the magnitude of vaccine-induced circulating and lung mucosal CD4+ and CD8+ T cell responses in both normal (CD4-replete) and CD4+ T cell deficient animals, including polyfunctional T cell responses.
2075 22349523 The presence of CD40L alone was insufficient to enhance or restore CD4+ T cell responses in CD4-ablated animals; however, in partially depleted animals, co-immunization with Ag85B and CD40L was capable of eliciting enhanced T cell responses, similar to those observed in normal animals, when compared to those given vaccine antigen alone.
2076 22349523 In summary, these findings show that CD40L has the capacity to enhance the magnitude of vaccine-induced polyfunctional T cell responses in CD4+ T cell deficient mice, and warrants further study as an adjuvant for immunization against opportunistic pathogens in individuals with CD4+ T cell deficiency.
2077 22349523 CD40 ligand enhances immunogenicity of vector-based vaccines in immunocompetent and CD4+ T cell deficient individuals.
2078 22349523 CD40 ligand (CD40L or CD154), a member of the tumor necrosis factor superfamily (TNFSF), is an important co-stimulatory molecule and, through interactions with its cognate receptor CD40, plays a pivotal role in the generation of host immune responses.
2079 22349523 Exploitation of CD40L and its receptor CD40 could provide a means to enhance and potentially restore protective immune responses in CD4+ T cell deficiency.
2080 22349523 Co-immunization of mice with CD40L and Ag85B by intranasal or intramuscular prime-boosting led to route-dependent enhancement of the magnitude of vaccine-induced circulating and lung mucosal CD4+ and CD8+ T cell responses in both normal (CD4-replete) and CD4+ T cell deficient animals, including polyfunctional T cell responses.
2081 22349523 The presence of CD40L alone was insufficient to enhance or restore CD4+ T cell responses in CD4-ablated animals; however, in partially depleted animals, co-immunization with Ag85B and CD40L was capable of eliciting enhanced T cell responses, similar to those observed in normal animals, when compared to those given vaccine antigen alone.
2082 22349523 In summary, these findings show that CD40L has the capacity to enhance the magnitude of vaccine-induced polyfunctional T cell responses in CD4+ T cell deficient mice, and warrants further study as an adjuvant for immunization against opportunistic pathogens in individuals with CD4+ T cell deficiency.
2083 22349523 CD40 ligand enhances immunogenicity of vector-based vaccines in immunocompetent and CD4+ T cell deficient individuals.
2084 22349523 CD40 ligand (CD40L or CD154), a member of the tumor necrosis factor superfamily (TNFSF), is an important co-stimulatory molecule and, through interactions with its cognate receptor CD40, plays a pivotal role in the generation of host immune responses.
2085 22349523 Exploitation of CD40L and its receptor CD40 could provide a means to enhance and potentially restore protective immune responses in CD4+ T cell deficiency.
2086 22349523 Co-immunization of mice with CD40L and Ag85B by intranasal or intramuscular prime-boosting led to route-dependent enhancement of the magnitude of vaccine-induced circulating and lung mucosal CD4+ and CD8+ T cell responses in both normal (CD4-replete) and CD4+ T cell deficient animals, including polyfunctional T cell responses.
2087 22349523 The presence of CD40L alone was insufficient to enhance or restore CD4+ T cell responses in CD4-ablated animals; however, in partially depleted animals, co-immunization with Ag85B and CD40L was capable of eliciting enhanced T cell responses, similar to those observed in normal animals, when compared to those given vaccine antigen alone.
2088 22349523 In summary, these findings show that CD40L has the capacity to enhance the magnitude of vaccine-induced polyfunctional T cell responses in CD4+ T cell deficient mice, and warrants further study as an adjuvant for immunization against opportunistic pathogens in individuals with CD4+ T cell deficiency.
2089 22355605 Demonstration of the CD40-ligand interactions may provide a new possible perspective on molecular mechanisms of borrelial BBB translocation process.
2090 22536391 MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules.
2091 22536391 The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype.
2092 22561311 We have previously reported that defined cocktails of cytokines, involving TNFα and IFNγ, induce mature type-1 polarized DCs (DC1s) which produce strongly elevated levels of IL-12 and CXCL10/IP10 upon CD40 ligation compared to "standard" PGE₂-matured DCs (sDCs; matured with IL-1β, IL-6, TNFα, and PGE₂) and show higher CTL-inducing activity.
2093 22561311 Restimulated lymphocytes, or their culture supernatants, enhanced the maturation status of immature (i)DCs, elevating their expression of CD80, CD83 and CCR7, and the ability to produce IL-12p70 and CXCL10 upon subsequent CD40 ligation.
2094 22561311 We have previously reported that defined cocktails of cytokines, involving TNFα and IFNγ, induce mature type-1 polarized DCs (DC1s) which produce strongly elevated levels of IL-12 and CXCL10/IP10 upon CD40 ligation compared to "standard" PGE₂-matured DCs (sDCs; matured with IL-1β, IL-6, TNFα, and PGE₂) and show higher CTL-inducing activity.
2095 22561311 Restimulated lymphocytes, or their culture supernatants, enhanced the maturation status of immature (i)DCs, elevating their expression of CD80, CD83 and CCR7, and the ability to produce IL-12p70 and CXCL10 upon subsequent CD40 ligation.
2096 22592077 The immunosuppressive factors IL-10, TGF-β, and VEGF do not affect the antigen-presenting function of CD40-activated B cells.
2097 22684115 The enhanced expression of MHC II and CD40 on DCs after incubation with amphiphilic polyanhydride particles, and the increased secretion of IL-6, TNF-α, and IL-12p40 by hydrophobic polyanhydride particles exemplified the chemistry-dependent activation of DCs by sham-coated particles.
2098 22791285 In human BDCA1+ and monocyte-derived DCs, CD40 and mannose receptor targeted antibody conjugates to early endosomes, whereas DEC205 targeted antigen primarily to late compartments.
2099 22791285 This did not reflect DC activation by CD40, but rather its relatively poor uptake or intra-endosomal degradation compared with mannose receptor or DEC205.
2100 22791285 In human BDCA1+ and monocyte-derived DCs, CD40 and mannose receptor targeted antibody conjugates to early endosomes, whereas DEC205 targeted antigen primarily to late compartments.
2101 22791285 This did not reflect DC activation by CD40, but rather its relatively poor uptake or intra-endosomal degradation compared with mannose receptor or DEC205.
2102 22829976 B-cell lymphoma 6 (Bcl-6) protein expression and the proportion of HLA-DR(+) or CD40(+) cells were higher in colonies of Th2 cell-stimulated myeloma cells.
2103 22829976 Furthermore, anti-HLA-DR or neutralizing CD40 antibody could prevent this increase in Bcl-6 expression and colony number.
2104 22829976 B-cell lymphoma 6 (Bcl-6) protein expression and the proportion of HLA-DR(+) or CD40(+) cells were higher in colonies of Th2 cell-stimulated myeloma cells.
2105 22829976 Furthermore, anti-HLA-DR or neutralizing CD40 antibody could prevent this increase in Bcl-6 expression and colony number.
2106 22904311 We previously demonstrated that DNA and protein covaccination converted naive T cells to Ag-specific iTregs by inducing CD11c+CD40(low)IL-10+ regulatory dendritic cells (DCregs).
2107 22904311 In this paper, we report that the event is initiated by coentry of sequence-matched DNA and protein immunogens into the same DC via caveolae-mediated endocytosis, which leads to inhibition of phosphorylation of caveolin-1 (Cav-1), the main component of caveolae, and upregulation of Tollip.
2108 22904311 Silencing either Cav-1 or Tollip blocks the negative signaling, leading to upregulated expression of CD40, downregulated production of IL-10, and loss of iTreg-inducing function.
2109 22904311 We previously demonstrated that DNA and protein covaccination converted naive T cells to Ag-specific iTregs by inducing CD11c+CD40(low)IL-10+ regulatory dendritic cells (DCregs).
2110 22904311 In this paper, we report that the event is initiated by coentry of sequence-matched DNA and protein immunogens into the same DC via caveolae-mediated endocytosis, which leads to inhibition of phosphorylation of caveolin-1 (Cav-1), the main component of caveolae, and upregulation of Tollip.
2111 22904311 Silencing either Cav-1 or Tollip blocks the negative signaling, leading to upregulated expression of CD40, downregulated production of IL-10, and loss of iTreg-inducing function.
2112 22904313 Peripheral blood monocytes were treated with GM-CSF and IL-4 to yield immature DCs, which were matured by addition of LPS and CD40 ligand (CD40L), with or without ESAT-6.
2113 22904313 ESAT-6 inhibited LPS/CD40L-induced DC expression of costimulatory molecules, reduced DC-stimulated allogeneic T cell proliferation and IL-2 and IFN-γ production, and enhanced IL-17 production.
2114 22904313 ESAT-6 inhibited LPS/CD40L-induced DC production of IL-12 and enhanced that of IL-23 and IL-1β, without affecting secretion of TNF-α, IL-6, or IL-8 through specific interaction with immature DCs.
2115 22904313 Medium from ESAT-6-conditioned DCs increased IL-17 and reduced IFN-γ production by T cells stimulated with anti-CD3 plus anti-CD28, and ESAT-6-induced IL-17 production was blocked by neutralizing both IL-23 and IL-1β.
2116 22904313 ESAT-6 reduced LPS/CD40L-stimulated transcription of IL-12p35 and enhanced that of IL-23p19 through inhibition of IFN regulatory factor-1 and upregulation of activating transcription factor-2 and c-Jun, transcriptional regulators of IL-12p35 and IL-23p19, respectively.
2117 22904313 We conclude that ESAT-6 increases DC production of IL-23 and IL-1β while inhibiting that of IL-12, thus enhancing Th17 at the expense of protective Th1 responses.
2118 22906944 The production of cytokine IL-12 and TNF-α secreted by BMDCs in the presence of MENK was assayed with ELISA and key surface markers of CD40, CD86, CD83 and MHC-II on the BMDCs were analyzed with use of flow cytometry (FCM).
2119 22926059 Like other TNF family members, in vivo and in vitro activity of CD40L requires a homotrimeric configuration, and growing evidence suggests that bioactivity depends on higher-order clustering of CD40.
2120 22927979 RB51-infected wild type BMDCs were mature and activated as shown by significantly up-regulated expression of CD40, CD80, CD86, MHC-I, and MHC-II.
2121 22927979 RB51-infected WT BMDCs also stimulated the proliferation of CD4(+) and CD8(+) T cells compared to uninfected WT BMDCs.
2122 22948808 Phenotype and function of protective, CD4-independent CD8 T cell memory.
2123 22948808 While the need for CD4 T cells in the generation of CD8 T cell memory has been well documented, the mechanism underlying their requirement remains unknown.
2124 22948808 Here, we detail an immunization method capable of generating CD8 memory T cells that are indifferent to CD4 T cell help.
2125 22948808 Using a subunit vaccination that combines polyIC and an agonistic CD40 antibody, we program protective CD4-independent CD8 T cell memory.
2126 22948808 When cells generated by combined polyIC/CD40 immunization are compared to cells produced following a CD4-dependent vaccination, Listeria monocytogenes, they display dramatic differences, both phenotypically and functionally.
2127 22948808 The memory cells generated in a CD4-deficient host by polyIC/CD40 immunization provide protection against secondary infectious challenge, whereas cells generated by LM immunization in the same environment do not.
2128 22948808 Interestingly, combined polyIC/CD40 immunization generates long-term memory cells with low Blimp-1 and elevated Eomes expression despite high expression of Blimp-1 during the primary response.
2129 22948808 The potency of combined polyIC/CD40 to elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be considered as a vaccine adjuvant in clinical situations where CD4 responses/numbers are compromised.
2130 22948808 Phenotype and function of protective, CD4-independent CD8 T cell memory.
2131 22948808 While the need for CD4 T cells in the generation of CD8 T cell memory has been well documented, the mechanism underlying their requirement remains unknown.
2132 22948808 Here, we detail an immunization method capable of generating CD8 memory T cells that are indifferent to CD4 T cell help.
2133 22948808 Using a subunit vaccination that combines polyIC and an agonistic CD40 antibody, we program protective CD4-independent CD8 T cell memory.
2134 22948808 When cells generated by combined polyIC/CD40 immunization are compared to cells produced following a CD4-dependent vaccination, Listeria monocytogenes, they display dramatic differences, both phenotypically and functionally.
2135 22948808 The memory cells generated in a CD4-deficient host by polyIC/CD40 immunization provide protection against secondary infectious challenge, whereas cells generated by LM immunization in the same environment do not.
2136 22948808 Interestingly, combined polyIC/CD40 immunization generates long-term memory cells with low Blimp-1 and elevated Eomes expression despite high expression of Blimp-1 during the primary response.
2137 22948808 The potency of combined polyIC/CD40 to elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be considered as a vaccine adjuvant in clinical situations where CD4 responses/numbers are compromised.
2138 22948808 Phenotype and function of protective, CD4-independent CD8 T cell memory.
2139 22948808 While the need for CD4 T cells in the generation of CD8 T cell memory has been well documented, the mechanism underlying their requirement remains unknown.
2140 22948808 Here, we detail an immunization method capable of generating CD8 memory T cells that are indifferent to CD4 T cell help.
2141 22948808 Using a subunit vaccination that combines polyIC and an agonistic CD40 antibody, we program protective CD4-independent CD8 T cell memory.
2142 22948808 When cells generated by combined polyIC/CD40 immunization are compared to cells produced following a CD4-dependent vaccination, Listeria monocytogenes, they display dramatic differences, both phenotypically and functionally.
2143 22948808 The memory cells generated in a CD4-deficient host by polyIC/CD40 immunization provide protection against secondary infectious challenge, whereas cells generated by LM immunization in the same environment do not.
2144 22948808 Interestingly, combined polyIC/CD40 immunization generates long-term memory cells with low Blimp-1 and elevated Eomes expression despite high expression of Blimp-1 during the primary response.
2145 22948808 The potency of combined polyIC/CD40 to elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be considered as a vaccine adjuvant in clinical situations where CD4 responses/numbers are compromised.
2146 22948808 Phenotype and function of protective, CD4-independent CD8 T cell memory.
2147 22948808 While the need for CD4 T cells in the generation of CD8 T cell memory has been well documented, the mechanism underlying their requirement remains unknown.
2148 22948808 Here, we detail an immunization method capable of generating CD8 memory T cells that are indifferent to CD4 T cell help.
2149 22948808 Using a subunit vaccination that combines polyIC and an agonistic CD40 antibody, we program protective CD4-independent CD8 T cell memory.
2150 22948808 When cells generated by combined polyIC/CD40 immunization are compared to cells produced following a CD4-dependent vaccination, Listeria monocytogenes, they display dramatic differences, both phenotypically and functionally.
2151 22948808 The memory cells generated in a CD4-deficient host by polyIC/CD40 immunization provide protection against secondary infectious challenge, whereas cells generated by LM immunization in the same environment do not.
2152 22948808 Interestingly, combined polyIC/CD40 immunization generates long-term memory cells with low Blimp-1 and elevated Eomes expression despite high expression of Blimp-1 during the primary response.
2153 22948808 The potency of combined polyIC/CD40 to elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be considered as a vaccine adjuvant in clinical situations where CD4 responses/numbers are compromised.
2154 22948808 Phenotype and function of protective, CD4-independent CD8 T cell memory.
2155 22948808 While the need for CD4 T cells in the generation of CD8 T cell memory has been well documented, the mechanism underlying their requirement remains unknown.
2156 22948808 Here, we detail an immunization method capable of generating CD8 memory T cells that are indifferent to CD4 T cell help.
2157 22948808 Using a subunit vaccination that combines polyIC and an agonistic CD40 antibody, we program protective CD4-independent CD8 T cell memory.
2158 22948808 When cells generated by combined polyIC/CD40 immunization are compared to cells produced following a CD4-dependent vaccination, Listeria monocytogenes, they display dramatic differences, both phenotypically and functionally.
2159 22948808 The memory cells generated in a CD4-deficient host by polyIC/CD40 immunization provide protection against secondary infectious challenge, whereas cells generated by LM immunization in the same environment do not.
2160 22948808 Interestingly, combined polyIC/CD40 immunization generates long-term memory cells with low Blimp-1 and elevated Eomes expression despite high expression of Blimp-1 during the primary response.
2161 22948808 The potency of combined polyIC/CD40 to elicit CD8+ T cell memory in the absence of CD4 T cells suggests that it could be considered as a vaccine adjuvant in clinical situations where CD4 responses/numbers are compromised.
2162 23056548 To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ).
2163 23056548 Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1-PSMA cells pretreated with Ad5-IFNγ as target cells.
2164 23060228 BMDCs in vitro and DCs in vivo also display upregulation of activation markers CD80 and CD86 when treated with microparticles, again with no difference in conjugated antibodies, even the agonistic CD40 antibody.
2165 23129076 HIV antibody and DNA polymerase chain reaction were negative, and the patient had normal immunophenotype, mitogen stimulation response, CD40 ligand and inducible costimulator expression, transmembrane activator and CAML interactor sequencing, genomic analysis, and fluorescent in situ hybridization for deletions at 22q11.2.
2166 23223173 To determine whether CD40 DNA vaccine targeting the encoded CD40 directly to dendritic cells would improve the efficacy of the vaccination against self-protein CD40, we utilized a plasmid encoding a single-chain Fv antibody specific for the dendritic cell-restricted antigen-uptake receptor DEC205 (scDEC), the target gene CD40, and the adjuvant tetanus sequence p30.
2167 23238593 A vaccine platform has been created by attaching the target-associated antigen (TAA) for the vaccine to the extracellular domain (ecd) of the potent immunostimulatory signal CD40 ligand (CD40L).
2168 23238593 Attachment of the TAA to the CD40L promotes uptake of the TAA into dendritic cells (DCs), binding to Class I as well as Class II MHC leading to presentation of the TAA on the DCs, expansion of the TAA-specific B cell and CD8 effector T-cell lymphocytes, and induction of a memory response.
2169 23246902 Phenotypic maturation of BMDCs was confirmed by conventional scanning electron microscopy (SEM), flow cytometry (FCM) and functional maturation by transmission electron microscopy (TEM), cytochemistry assay, Acid phosphatase (ACP) activity, FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA).We found that RGP up-regulated the expression of CD40, CD80, CD83, CD86 and MHC II molecules of BMDCs, down-regulated pinocytosis and phagocytosis activity, induced IL-12 and TNF-α production of BMDCs.
2170 23266830 The roles of various immune-related pathways such as type-I IFN, CD40 costimulation, CD4 T cells, TLRs and the MDA5 RNA helicase were examined.
2171 23376446 Expression levels of INF-γ and IL-4, which are characteristic cytokines secreted during Th1-like and Th2-like immune responses, respectively, were unchanged in vaccinated animals as compared to control animals.
2172 23376446 Expression levels of TNF-α and some related molecules, such as ADAM17, FasL, CD40 and TRAF3 were also elevated.
2173 23455713 Once there, primed T cells became dysfunctional and underwent antigen-driven, interferon-γ (IFN-γ)- and Fas ligand (FasL)-mediated apoptosis, resulting in hyporesponsiveness to subsequent vaccination.
2174 23455713 Provision of CD40-specific antibody, Toll-like receptor 7 (TLR7) agonist and interleukin-2 (IL-2) reduced T cell apoptosis but did not prevent vaccination-site sequestration.
2175 23457630 TRIF is required for TLR4 mediated adjuvant effects on T cell clonal expansion.
2176 23457630 Activation of TLR4 by its ligands is mediated by engagement of the adapter proteins MyD88 (myeloid differentiation factor 88) and TRIF (Toll-interleukin 1 receptor domain-containing adapter inducing interferon-beta).
2177 23457630 Previously, we showed that TRIF, but not MyD88, plays an important role in allowing TLR4 agonists to adjuvant early T cell responses.
2178 23457630 In this study, we investigated the T cell priming events that are regulated specifically by the TRIF signaling branch of TLR4.
2179 23457630 We found that TRIF deficiency prevented the TLR4 agonist lipid A from enhancing T cell proliferation and survival in an adoptive transfer model of T cell priming.
2180 23457630 Importantly, TRIF alone caused CD86 and CD40 upregulation on splenic DC, but both TRIF and MyD88 were required for CD80 upregulation.
2181 23457630 The impairment of T cell adjuvant effects and defective DC maturation in TRIF (lps/lps) mice after TLR4 stimulation was mainly due to loss of type I IFN production, indicating that type I interferons are central to TLR4's adjuvant effects.
2182 23460531 The list of antagonist agents acting on repressors under development includes anti-CTLA-4, anti-PD-1, anti-PD-L1 (B7-H1), anti-KIR, and anti-TGF-β.
2183 23460531 Agonist antibodies currently being investigated in clinical trials target CD40, CD137 (4-1BB), CD134 (OX40), and glucocorticoid-induced TNF receptor (GITR).
2184 23467777 The vaccine significantly enhanced the production of gamma interferon (IFN-γ) and interleukin 2 (IL-2) after one immunization and enhanced the production of IL-4 and IL-10 after two immunizations.
2185 23467777 In addition, real-time PCR indicated that the expression of major histocompatibility complex I (MHC-I), as well as that of CD40 and CD154 molecules, was significantly increased after one immunization, and the expressions of both MHC-I and MHC-II molecules were increased after two immunizations.
2186 23507086 Molecular pathways upregulated by MA-CNTs included IL6, CD40, dendritic cell maturation, tumor necrosis factor-(TNF)-α/TNFR1-2, NFKB signaling and T helper 1 chemokine pathways (CXCR3 and CCR5 ligand pathways).
2187 23507086 To confirm the results at protein level, the secretion of IL1β, TNFα, IL6 and IL10 by THP1 and primary monocytes was assessed by ELISA, corroborating gene-expression data.
2188 23615121 Targeting concatenated HIV antigens to human CD40 expands a broad repertoire of multifunctional CD4+ and CD8+ T cells.
2189 23620105 DCs were transfected with IDO small interfering RNA and mRNA encoding human telomerase reverse transcriptase (hTERT) or survivin, two universal tumour antigens.
2190 23620105 Silencing of IDO in DCs did not affect the expression of the co-stimulatory molecules CD80 and CD86, but enhanced the expression of the CCR7 and CD40 molecules.
2191 23620105 The immunisation with this novel DC cancer vaccine was well tolerated and all patients developed delayed-type hypersensitivity skin reaction and specific T-cell response against hTERT and survivin tumour antigens.
2192 23735481 In vitro experiments using mouse bone marrow-derived DC (BMDC) demonstrated that PSK induces DC maturation as shown by dose-dependent increase in the expression of CD80, CD86, MHCII, and CD40.
2193 23749374 In this study, we demonstrate that antiviral, LCMV-binding, non-neutralizing antibodies are needed, in addition to CD4(+) and CD8(+) T cells, to clear a high-dose LCMV infection in mice, in the absence of IL-10.
2194 23749374 The interaction between CD4(+) T cells and B cells in B-cell follicles via CD40/CD40L, in addition to class switch and/or somatic hypermutation, is crucial for viral control in the absence of IL-10.
2195 23750793 CD40 activation dramatically improves antigen presentation by normal and malignant B cells, efficiently inducing naive and memory CD4(+) and CD8(+) T-cell responses.
2196 23760241 Infection of B cells resulted in the significant upregulation of early markers of B cell activation and antigen presentation, including CD69, major histocompatibility complex class II (MHC-II), and CD40 in murine B cells or HLA-DR and CD40 in human B cells compared to mock-infected cells or cells treated with an inactivated RABV-based vaccine.
2197 23760241 Furthermore, primary B cells infected with a live RABV expressing ovalbumin were able to prime and stimulate naive CD4(+) OT-II T cells to proliferate and to secrete interleukin-2 (IL-2), demonstrating a functional consequence of B cell infection and activation by live RABV-based vaccine vectors.
2198 23761659 Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.
2199 23761659 CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity.
2200 23761659 In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of live Mycobacterium avium subsp. paratuberculosis and exogenous gamma interferon, interleukin 10, and transforming growth factor β.
2201 23761659 Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic).
2202 23761659 A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals.
2203 23761659 No effects of exogenous cytokines on CD40 or CD40L expression were observed.
2204 23761659 Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.
2205 23761659 CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity.
2206 23761659 In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of live Mycobacterium avium subsp. paratuberculosis and exogenous gamma interferon, interleukin 10, and transforming growth factor β.
2207 23761659 Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic).
2208 23761659 A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals.
2209 23761659 No effects of exogenous cytokines on CD40 or CD40L expression were observed.
2210 23761659 Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.
2211 23761659 CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity.
2212 23761659 In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of live Mycobacterium avium subsp. paratuberculosis and exogenous gamma interferon, interleukin 10, and transforming growth factor β.
2213 23761659 Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic).
2214 23761659 A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals.
2215 23761659 No effects of exogenous cytokines on CD40 or CD40L expression were observed.
2216 23761659 Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.
2217 23761659 CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity.
2218 23761659 In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of live Mycobacterium avium subsp. paratuberculosis and exogenous gamma interferon, interleukin 10, and transforming growth factor β.
2219 23761659 Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic).
2220 23761659 A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals.
2221 23761659 No effects of exogenous cytokines on CD40 or CD40L expression were observed.
2222 23761659 Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.
2223 23761659 CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity.
2224 23761659 In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of live Mycobacterium avium subsp. paratuberculosis and exogenous gamma interferon, interleukin 10, and transforming growth factor β.
2225 23761659 Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic).
2226 23761659 A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals.
2227 23761659 No effects of exogenous cytokines on CD40 or CD40L expression were observed.
2228 23761659 Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.
2229 23761659 CD40 and CD40 ligand (CD40L) have costimulatory effects as part of a complex series of events in host immunity.
2230 23761659 In this study, the expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolated from cattle with Johne's disease were measured on freshly isolated PBMCs and on cells cultured for 8, 24, and 72 h in the presence or absence of live Mycobacterium avium subsp. paratuberculosis and exogenous gamma interferon, interleukin 10, and transforming growth factor β.
2231 23761659 Results demonstrated greater CD40 and CD40L expression on fresh PBMCs obtained from animals in the clinical stage of disease (symptomatic) than those from healthy control animals or cows in the subclinical stage of disease (asymptomatic).
2232 23761659 A similar expression profile with greater magnitude was noted for cultured PBMCs, with increased CD40 expression after 8 and 24 h of culture and increased CD40L expression between 24 and 72 h on PBMCs obtained from clinically infected animals.
2233 23761659 No effects of exogenous cytokines on CD40 or CD40L expression were observed.
2234 23764536 The immunopotentiating activity of OmpA is mediated by its ability to bind and stimulate macrophages and up-regulate the surface expression of MHCII, CD80 and CD40, leading to activation of CD4(+) T cells to secrete cytokines and express chemokine receptor and IL-12Rβ2, thereby orchestrating the bridge between innate and adaptive immune responses.
2235 23774693 We demonstrated that LD1ED III possesses an inherent immunostimulation ability that can activate RAW 264.7 macrophage cells by up-regulating their expression of CD40, CD80, CD83, CD86 and MHC II, whereas D1ED III could not induce the up-regulation of these molecules.
2236 23781340 In this study, IFN-gamma treatment of bone marrow-derived DC, followed by incubation with the TLR2, TLR4, or TLR9 agonists, enhanced DC activation compared to TLR ligation alone.
2237 23781340 Most notably, the upregulation of CD40 with LPS stimulation and CD86 with CpG stimulation was observed in in vitro cultures.
2238 23781340 Similarly, IFN-gamma coinjected with TLR ligands was able to promote DC activation in vivo, with DCs migrating from the site of immunization to the popliteal lymph nodes demonstrating increased expression of CD80 and CD86.
2239 23799649 Afterwards, the investigation into the maturation activation on primary bone marrow-derived DCs (BMDCs) showed that both Man-LPD and Man-free LPD induced remarkable up-regulation of CD80, CD86 and CD40 on BMDCs.
2240 23804272 We have discovered a method to induce stable tolerogenic ability to dendritic cells ex vivo using a mixture of phosphorothioate-modified antisense DNA targeting the primary transcripts of CD40, CD80 and CD86.
2241 23816303 In the present study, we have used isolated purified B cells and in vivo studies to demonstrate that αGalCer and RA initiate a regulated expression of several genes essential for B cell activation and differentiation, such as Pax-5, Blimp-1, IRF-4 and activation-induced cytidine deaminase (Aid).
2242 23816303 Moreover, whereas αGalCer mainly increased the expression of Pax-5, CD40 and CD86 that are critical for B cell activation, RA predominantly increased CD138⁺ and Fas⁺-PNA⁺ B cells, which represent more advanced B cell differentiation.
2243 23935688 DsII-TN5 stimulated the expression of CD40, CD80, CD86, and IL-1 β in TCL-loaded DCs and downregulated the expression of TGF- β 1.
2244 24045575 The restricted development of IgA plasma cells in the first month was accompanied by reduced expression of the TI factor a proliferation-inducing ligand (APRIL) and its receptors TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) and B cell maturation antigen (BCMA) within isolated lymphoid follicles (ILFs).
2245 24045575 Conversely, TD mediators (CD40 ligand (CD40L) and CD40) were expressed within ILFs before 1 month and were not associated with IgA plasma cell generation.
2246 24095953 We have shown that IFN-α 1) up-regulates the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulates the rates of pinocytosis and phagocytosis by BMDCs as evidenced by the results of decreased ACP, and FITC-dextran bio-assay; 3) enhances the ability of BMDCs to drive T cell function; and 4) induces higher levels of IL-12 and TNF-α secreted by BMDCs.
2247 24135577 The vaccine, human papillomavirus peptides with Candida, demonstrated partial maturation effects on Langerhans cells indicated by significantly up-regulated CD40 (p=0.00007) and CD80 (p<0.00001) levels, and showed T-cell proliferative capacity (p<0.00001) when presented by Langerhans cells in vitro.
2248 24135577 The cytokine profile (IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-23Ap19, IFN-γ and TNF-α) of Langerhans cells treated with the vaccine or Candida alone showed that IL-12p40 mRNA was most frequently induced, and IL-12p70 protein was detected in the supernatants.
2249 24135577 The presence of pattern recognition receptors known to associate with Candida albicans (DC-SIGN, dectin-1, dectin-2, galectin-3, mincle, mannose receptor, Toll-like receptors-1, 2, 4, 6 and 9) were demonstrated in all subjects.
2250 24173626 In the present study, exosomes from CD40 ligand gene‑modified 3LL tumor cells (CD40L‑EXO) were identified to be more immunogenic compared with control‑EXO and lac Z-EXO.
2251 24198065 In addition, the molecule latent membrane protein 1 (LMP1), a viral mimic of the TNF superfamily receptor CD40, provides an alternative approach for the design of novel molecular adjuvants.
2252 24198065 Here, we discuss advances in the development of recombinant TNF superfamily ligands as adjuvants for HIV vaccines and as cancer immunotherapy, including the use of LMP1 and LMP1-CD40 chimeric fusion proteins to mimic constitutive CD40 signaling.
2253 24198065 In addition, the molecule latent membrane protein 1 (LMP1), a viral mimic of the TNF superfamily receptor CD40, provides an alternative approach for the design of novel molecular adjuvants.
2254 24198065 Here, we discuss advances in the development of recombinant TNF superfamily ligands as adjuvants for HIV vaccines and as cancer immunotherapy, including the use of LMP1 and LMP1-CD40 chimeric fusion proteins to mimic constitutive CD40 signaling.
2255 24227853 Vaccination with a fusion protein that introduces HIV-1 gag antigen into a multitrimer CD40L construct results in enhanced CD8+ T cell responses and protection from viral challenge by vaccinia-gag.
2256 24227853 CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8(+) T cell responses.
2257 24227853 To be active, CD40L must cluster CD40 receptors on responding cells.
2258 24227853 To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct.
2259 24227853 With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex.
2260 24227853 This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro.
2261 24227853 Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8(+) T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus.
2262 24227853 This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8(+) T cell responses or improve protection from vaccinia-Gag challenge.
2263 24227853 Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8(+) T cell responses.
2264 24227853 Vaccination with a fusion protein that introduces HIV-1 gag antigen into a multitrimer CD40L construct results in enhanced CD8+ T cell responses and protection from viral challenge by vaccinia-gag.
2265 24227853 CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8(+) T cell responses.
2266 24227853 To be active, CD40L must cluster CD40 receptors on responding cells.
2267 24227853 To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct.
2268 24227853 With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex.
2269 24227853 This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro.
2270 24227853 Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8(+) T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus.
2271 24227853 This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8(+) T cell responses or improve protection from vaccinia-Gag challenge.
2272 24227853 Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8(+) T cell responses.
2273 24227853 Vaccination with a fusion protein that introduces HIV-1 gag antigen into a multitrimer CD40L construct results in enhanced CD8+ T cell responses and protection from viral challenge by vaccinia-gag.
2274 24227853 CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8(+) T cell responses.
2275 24227853 To be active, CD40L must cluster CD40 receptors on responding cells.
2276 24227853 To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct.
2277 24227853 With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex.
2278 24227853 This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro.
2279 24227853 Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8(+) T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus.
2280 24227853 This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8(+) T cell responses or improve protection from vaccinia-Gag challenge.
2281 24227853 Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8(+) T cell responses.
2282 24227853 Vaccination with a fusion protein that introduces HIV-1 gag antigen into a multitrimer CD40L construct results in enhanced CD8+ T cell responses and protection from viral challenge by vaccinia-gag.
2283 24227853 CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8(+) T cell responses.
2284 24227853 To be active, CD40L must cluster CD40 receptors on responding cells.
2285 24227853 To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct.
2286 24227853 With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex.
2287 24227853 This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro.
2288 24227853 Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8(+) T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus.
2289 24227853 This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8(+) T cell responses or improve protection from vaccinia-Gag challenge.
2290 24227853 Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8(+) T cell responses.
2291 24227853 Vaccination with a fusion protein that introduces HIV-1 gag antigen into a multitrimer CD40L construct results in enhanced CD8+ T cell responses and protection from viral challenge by vaccinia-gag.
2292 24227853 CD40 ligand (CD40L, CD154) is a membrane protein that is important for the activation of dendritic cells (DCs) and DC-induced CD8(+) T cell responses.
2293 24227853 To be active, CD40L must cluster CD40 receptors on responding cells.
2294 24227853 To produce a soluble form of CD40L that clusters CD40 receptors necessitates the use of a multitrimer construct.
2295 24227853 With this in mind, a tripartite fusion protein was made from surfactant protein D (SPD), HIV-1 Gag as a test antigen, and CD40L, where SPD serves as a scaffold for the multitrimer protein complex.
2296 24227853 This SPD-Gag-CD40L protein activated CD40-bearing cells and bone marrow-derived DCs in vitro.
2297 24227853 Compared to a plasmid for Gag antigen alone (pGag), DNA vaccination of mice with pSPD-Gag-CD40L induced an increased number of Gag-specific CD8(+) T cells with increased avidity for major histocompatibility complex class I-restricted Gag peptide and improved vaccine-induced protection from challenge by vaccinia-Gag virus.
2298 24227853 This plasmid, pTrimer-Gag-CD40L, was only weakly active on CD40-bearing cells and did not elicit strong CD8(+) T cell responses or improve protection from vaccinia-Gag challenge.
2299 24227853 Overall, these results show the potential of a new vaccine design in which antigen is introduced into a construct that expresses a multitrimer soluble form of CD40L, leading to strongly protective CD8(+) T cell responses.
2300 24252697 In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40.
2301 24252697 PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II.
2302 24252697 In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes.
2303 24319176 Clinical trials including CLL vaccines, CXCR4 antagonists, and adoptive cellular immunotherapies such as chimeric antigen receptor-modified T cells, CD40 ligand gene therapy, and the immunomodulatory drug lenalidomide are ongoing.
2304 24338222 In addition, we assessed the capacity of activated DCs to induce cytokine production and proliferation of lymphocytes.Listeria-derived protein fractions induced fully mature DCs expressing high costimulatory molecules such as CD80, CD86 and CD40.
2305 24343727 Using flow cytometry, we showed that rSjcPRMT1 slightly upregulated the expression of CD40, CD80, CD86, and MHC-II molecules of mouse bone marrow-derived dendritic cell (BMDC), indicating that rSjcPRMT1 could induce mouse BMDC to mature and, therefore, activate their immune response.
2306 24349212 Surface expression of activation markers on macrophages, including CD40, CD69, and CD86, was increased following PorB stimulation in vitro.
2307 24349212 Interestingly, some upregulation of CD54 and CD69 was still observed in macrophages obtained from TLR2 KO mice, indicating a possible non-TLR2 mediated activation pathway induced by PorB.
2308 24357081 The titers of serum HA-specific antibodies were determined by ELISA, and the expression levels of the cytokines IL-2, IL-4, IL-6 and TNF-α were determined by real-time PCR.
2309 24357081 The results showed that CD40 as a molecular adjuvant significantly enhanced the production of serum anti-HA antibodies and increased the levels of the Th2 cytokines IL-4 and IL-6, suggesting that co-immunization with CD40 upregulated the humoral immune responses to the DNA vaccine in BALB/c mice.
2310 24455776 We have found that LDN enhances maturation of BMDCs as evidenced by 1) up-regulating the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulating the rates of pinocytosis and phagocytosis accompanied by the results of decreased ACP, and FITC-dextran bio-assay; 3) mounting potential of BMDCs to drive T cell; and 4) inducing secretion of higher levels of IL-12 and TNF-α.
2311 24475289 Spores promoted activation of antigen presenting cells as demonstrated by the upregulation of MHC and CD40 molecules and enhanced secretion of pro-inflammatory cytokines by murine dendritic cells.
2312 24475289 In addition, in vivo studies indicated a direct role of the innate immunity on the immunomodulatory properties of B. subtilis spores, as demonstrated by the lack of adjuvant effects on MyD88 and TLR2 knockout mouse strains.
2313 24489846 Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1) to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1), on B cells to enhance B cell activation and RABV-specific antibody responses.
2314 24489846 While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV), rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells.
2315 24498563 Helper cell-independent antitumor activity of potent CD8+ T cell epitope peptide vaccines is dependent upon CD40L.
2316 24498563 Thus, some peptide vaccines are capable of activating CD8+ T-cell responses, even in the absence of CD4+ T-cell epitopes or dendritic cell (DC)-activating adjuvants.
2317 24498563 Using CT26 and ovalbumin-expressing B16 murine allograft tumor models, we found that the antitumor effect of helper cell-independent CD8 T-cell peptide vaccines is inhibited by the blockade of CD40 ligand (CD40L) in vivo.
2318 24498563 Furthermore, in vitro stimulation with antigenic peptides of cells derived from immunized mice induced the expression of CD40L on the surface of CD8+ T cells and fostered DC maturation, an effect that was partially inhibited by CD40L-blocking antibodies.
2319 24498563 Interestingly, CD40L blockade also inhibited CD8+ T-cell responses, even in the presence of fully mature DCs, suggesting a role for CD40L not only in promoting DC maturation but also in mediating CD8+ T-cell co-stimulation.
2320 24498563 Importantly, these potent peptides share features with bona fide CD4 epitopes, since they foster responses against less immunogenic CD8+ T-cell epitopes in a CD40L-dependent manner.
2321 24498563 The analysis of peptides used for the vaccination of cancer patients in clinical trials showed that these peptides also induce the expression of CD40L on the surface of CD8+ T cells.
2322 24498563 Taken together, these results suggest that CD40L expression induced by potent CD8+ T-cell epitopes can activate antitumor CD8+ T-cell responses, potentially amplifying the immunological responses to less immunogenic CD8+ T-cell epitopes and bypassing the requirement for CD4+ helper T cells in vaccination protocols.
2323 24502939 Immature myeloid (m)DCs circulating in the blood of cattle have been defined as lineage negative (Lin(-))MHCII(+)CD11c(+)CD205(+) cells.
2324 24502939 Lin(-)MHCII(+)CD11c(+)CD205(+) mDCs (0.2% blood mononuclear cells) isolated from bovine blood were heterogeneous in cell size and CD205 expression.
2325 24502939 Using highspeed cell sorting, Lin(-)MHCII(+)CD11c(+)CD205(+) DCs were sorted into CD205(Hi) and CD205(Lo) subpopulations which were phenotypically distinct and differed significantly (P<0.01) in TLR gene expression.
2326 24502939 T cell activation by CD205(Lo) mDCs was associated with differential up-regulation of CD40, CD80, CD86 and TGFβ1 gene expression when compared to CD205(Hi) mDCs.
2327 24502939 In conclusion, two phenotypically and functionally distinct CD11c(+)CD205(+) mDCs were isolated from blood that had an equal capacity to acquire antigen but markedly different capacities to activate T cells.
2328 24507356 The results showed that the treatment of macrophages with CS3 could not only increase the nitric oxide (NO) release and the cytokines TNF-α, IL-6 and IL-1β production significantly, but also enhance the inducible NOS (iNOS) expression, NF-κBp65 nuclear translocation, Erk1/2 and SAPK/JNK phosphorylation.
2329 24507356 The combination of CS3 with GM-CSF upregulated immature BMDCs to express major histocompatibility complex II (MHCII) and CD11c surface markers, CD40, CD80 and CD86 costimulatory molecules, as well as the cytokines of IL-12p70 and IL-6.
2330 24530933 Vaccinated fishes registered a significant increase in the expression of TNFR-1, FasL, IRF7, TLR2, IL-1b and CD40 gene transcripts when compared to the control group.
2331 24532579 In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists.
2332 24532579 Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity.
2333 24532579 NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation.
2334 24532579 Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity.
2335 24532579 Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell-mediated immune response.
2336 24579458 We found that this peptide induced the expression of T-bet and TATA box binding protein-associated factor that can induce the chromatin remodeling of ifn-gamma gene, and as a result induced Th1 differentiation even in the absence of IFN-gamma and IL-12.
2337 24579458 Next, we established an in vitro CTL differentiation system using Peptide-25, Peptide-25 specific CD4+ T cells, OVA specific CD8+ T cells and splenic DC.
2338 24579458 By using this system, we found that CD4+ T cells activated DC even in the absence of IFN-gamma and CD40 ligand association, and the activated DC induced the functional differentiation of CTL.
2339 24596571 Pre-treating mice with an antibody against the IL-10 receptor prior to vaccination results in DC that up-regulate CD40, CD80, and CD86 and promote stronger IFNγ+ T cell responses.
2340 24659689 Compared to wild-type, a hip1 mutant strain of M. tuberculosis induced enhanced levels of the key Th1-inducing cytokine IL-12, as well as other proinflammatory cytokines (IL-23, IL-6, TNF-α, IL-1β, and IL-18) in DCs via MyD88- and TLR2/9-dependent pathways, indicating that Hip1 restricts optimal DC inflammatory responses.
2341 24659689 Infection with the hip1 mutant also induced higher levels of MHC class II and costimulatory molecules CD40 and CD86, indicating that M. tuberculosis impairs DC maturation through Hip1.
2342 24664420 Direct T cell activation via CD40 ligand generates high avidity CD8+ T cells capable of breaking immunological tolerance for the control of tumors.
2343 24664420 CD40 and CD40 ligand (CD40L) are costimulatory molecules that play a pivotal role in the proinflammatory immune response.
2344 24664420 Primarily expressed by activated CD4+ T cells, CD40L binds to CD40 on antigen presenting cells (APCs), thereby inducing APC activation.
2345 24664420 Although p53 and GP100 are self-antigens that generate low affinity antigen-specific CD8+ T cells, studies have shown that their functional avidity can be improved with CD40L-expressing APCs.
2346 24664420 Furthermore, we showed that in vitro stimulation with irradiated tumor cells expressing both TAA and CD40L improved the functional avidity of antigen-specific CD8+ T cells.
2347 24664420 Thus, our data show that vaccination with TAA/CD40L DNA can induce potent antitumor effects against TAA-expressing tumors through the generation of better functioning antigen-specific CD8+ T cells.
2348 24664420 Direct T cell activation via CD40 ligand generates high avidity CD8+ T cells capable of breaking immunological tolerance for the control of tumors.
2349 24664420 CD40 and CD40 ligand (CD40L) are costimulatory molecules that play a pivotal role in the proinflammatory immune response.
2350 24664420 Primarily expressed by activated CD4+ T cells, CD40L binds to CD40 on antigen presenting cells (APCs), thereby inducing APC activation.
2351 24664420 Although p53 and GP100 are self-antigens that generate low affinity antigen-specific CD8+ T cells, studies have shown that their functional avidity can be improved with CD40L-expressing APCs.
2352 24664420 Furthermore, we showed that in vitro stimulation with irradiated tumor cells expressing both TAA and CD40L improved the functional avidity of antigen-specific CD8+ T cells.
2353 24664420 Thus, our data show that vaccination with TAA/CD40L DNA can induce potent antitumor effects against TAA-expressing tumors through the generation of better functioning antigen-specific CD8+ T cells.
2354 24664420 Direct T cell activation via CD40 ligand generates high avidity CD8+ T cells capable of breaking immunological tolerance for the control of tumors.
2355 24664420 CD40 and CD40 ligand (CD40L) are costimulatory molecules that play a pivotal role in the proinflammatory immune response.
2356 24664420 Primarily expressed by activated CD4+ T cells, CD40L binds to CD40 on antigen presenting cells (APCs), thereby inducing APC activation.
2357 24664420 Although p53 and GP100 are self-antigens that generate low affinity antigen-specific CD8+ T cells, studies have shown that their functional avidity can be improved with CD40L-expressing APCs.
2358 24664420 Furthermore, we showed that in vitro stimulation with irradiated tumor cells expressing both TAA and CD40L improved the functional avidity of antigen-specific CD8+ T cells.
2359 24664420 Thus, our data show that vaccination with TAA/CD40L DNA can induce potent antitumor effects against TAA-expressing tumors through the generation of better functioning antigen-specific CD8+ T cells.
2360 24671554 Eagan and Rd LOS had a lower capacity to induce the expression of ICAM-1, CD40, CD58, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) compared to LPS.
2361 24684292 Blood mDC had increased expression of MHC class II, CCR7 and CD40, whereas in lymph nodes these markers were significantly decreased, indicating that acute infection induced maturation of mDC in blood but resulted in accumulation of immature mDC in lymph nodes.
2362 24761845 The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods.
2363 24766519 Prominent up-regulation of co-stimulatory molecules CD40, CD80 and CD86 was also observed in response to MIP.
2364 24766519 With the help of pharmacological inhibitors and Toll-like receptor (TLR) -deficient macrophages, we observed the role of TLR2, TLR4 and intracellular TLRs in MIP-mediated macrophage activation.
2365 24771135 We show that the ability of exogenous DCs to trigger this pathway obviates CD40 signaling and CD4(+) T-cell help and depends on a preceding maturation step.
2366 24771135 In c-myc-transgenic mice developing spontaneous lymphomas, injection of unpulsed DCs caused NK-cell activation and induced CD8(+) T cells capable of recognizing the lymphoma cells.
2367 24825342 Topical rather than intradermal application of the TLR7 ligand imiquimod leads to human dermal dendritic cell maturation and CD8+ T-cell cross-priming.
2368 24825342 Moreover, Aldara-treated DCs showed highest levels of the costimulatory molecules CD86, CD83, CD40, and CD70.
2369 24825342 When combined with intradermal peptide vaccination, Aldara-stimulated DCs showed enhanced cross-presentation of the melanoma antigen MART-1, which resulted in increased priming and activation of MART-1-specific CD8(+) T cells.
2370 24846569 Pretreatment with WapA-GST also increased LPS-induced proinflammatory cytokine production by DCs, including IL-12, IL-6 and TNF-α.
2371 24846569 Furthermore, expression of the DC maturation markers CD80/86, CD40 and MHC II was also increased by WapA pretreatment.
2372 24861251 The functional maturation was confirmed by an acid phosphatase (ACP) activity test, FITC-dextran bio-assay, test of 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), labeled CD4(+)T cell proliferation and enzyme-linked immunosorbent assay (ELISA).
2373 24861251 We determined that thymopentin up-regulated the expression of CD40, CD80, CD86, CD83, and MHC II molecules on BMDCs, down-regulated phagocytosis of BMDCs, increased BMDCs driven CD4(+)T cell proliferation, and enhanced BMDC production of IL-12 and TNF-α.
2374 24911024 Systemic administration of fucoidan induced up-regulation of CD40, CD80 and CD86 expression and production of IL-6, IL-12 and TNF-α in spleen cDCs.
2375 24911024 Fucoidan also promoted the generation of IFN-γ-producing Th1 and Tc1 cells in an IL-12-dependent manner.
2376 24911024 Moreover, fucoidan enhanced OVA-induced up-regulation of MHC class I and II on spleen cDCs and strongly prompted the proliferation of OVA-specific CD4 and CD8 T cells.
2377 24928989 CD40 ligand preferentially modulates immune response and enhances protection against influenza virus.
2378 24928989 Adenoviral vectors secreting NP-CD40L fusion protein (denoted as rAd-SNP40L) afforded full protection of immunocompetent and immunocompromised mice (CD40L(-/-) and CD4(-/-)) against lethal influenza infection.
2379 24928989 Data generated from CD40L(-/-) and CD4(-/-) mice revealed that the protection was indeed CD40L mediated but CD4(+) T cell independent, demonstrating the viability of the fusion Ags in protecting immunodeficient hosts.
2380 24942994 We hereby proved that LJP markedly induced maturation of BMDCs with the data of decreased the number of lysosomes, upregulated expression of CD80, CD83, CD86, CD40 and MHC II key membrane molecules on BMDCs, downregulated phagocytosis, enriched production of IL-12 and TNF-α secreted by BMDCs.
2381 24945624 Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-α, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC), while leaving secreted levels of TGF-β unchanged.
2382 24945624 Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-γ and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP.
2383 24945624 Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-α compared to mice infected with BCG-GFP.
2384 24962751 The results demonstrated that rTs-Hsp70 activated DC maturation that was characterized by the secretion of IL-1β, IL-12p70, TNF-α, and IL-6 and the increased surface expression of CD11c, MHC II, CD40, CD80, and CD86.
2385 24962751 The rTs-Hsp70-activated DCs enabled the stimulation, proliferation and secretion of Th1/2 cytokines (i.e., INF-γ, IL-2, IL-4 and IL-6) in CD4(+) T cells from T. spiralis-infected mice.
2386 24962751 This partial protection was correlated with Th1 and Th2 mixed anti-Ts-Hsp70-specific immune responses that included high titers of total IgG, IgG1 and IgG2a and increased levels of Th1/2 cytokines (i.e., IFN-γ, IL-2, IL-4, IL-6).
2387 24992166 Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.
2388 24992166 The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and natural killer cells.
2389 25035957 Nucleoprotein (NP)-specific CD8(+) T cells encountered antigen on CD40-licensed, CD70-expressing, CD103(-)CD11b(hi) dendritic cells (DCs) at later times in the primary response.
2390 25035957 As a consequence, they maintained CD25 expression and responded to interleukin-2 (IL-2) and CD27, which together programmed their robust secondary proliferative capacity and interferon-γ (IFN-γ)-producing ability.
2391 25035957 In contrast, polymerase (PA)-specific CD8(+) T cells did not encounter antigen-bearing, CD40-activated DCs at later times in the primary response, did not receive CD27 and CD25 signals, and were not programmed to become memory CD8(+) T cells with strong proliferative and cytokine-producing ability.
2392 25035957 Nucleoprotein (NP)-specific CD8(+) T cells encountered antigen on CD40-licensed, CD70-expressing, CD103(-)CD11b(hi) dendritic cells (DCs) at later times in the primary response.
2393 25035957 As a consequence, they maintained CD25 expression and responded to interleukin-2 (IL-2) and CD27, which together programmed their robust secondary proliferative capacity and interferon-γ (IFN-γ)-producing ability.
2394 25035957 In contrast, polymerase (PA)-specific CD8(+) T cells did not encounter antigen-bearing, CD40-activated DCs at later times in the primary response, did not receive CD27 and CD25 signals, and were not programmed to become memory CD8(+) T cells with strong proliferative and cytokine-producing ability.
2395 25048786 A variety of other immunotherapies are in development, including CLL vaccines, CD40 ligand therapies, and monoclonal antibody immune checkpoint blockade.
2396 25068589 Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles.
2397 25068703 Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8(+) T cell response: a comparative study.
2398 25068703 These cell-surface molecules, including CD40, a TNF-α family receptor, DEC-205, a C-type lectin receptor and CD11c, an integrin receptor, were targeted by means of specific monoclonal antibodies (mAbs) coupled to the NP.
2399 25068703 We observed a small but significantly improved internalization of CD40-targeted NP compared to DEC-205 or CD11c targeted NP.
2400 25068703 Moreover, subcutaneous vaccination with CD40, DEC-205 and CD11c-targeted NP consistently showed higher efficacy than non-targeted NP in stimulating CD8+ T cell responses.
2401 25068703 Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8(+) T cell response: a comparative study.
2402 25068703 These cell-surface molecules, including CD40, a TNF-α family receptor, DEC-205, a C-type lectin receptor and CD11c, an integrin receptor, were targeted by means of specific monoclonal antibodies (mAbs) coupled to the NP.
2403 25068703 We observed a small but significantly improved internalization of CD40-targeted NP compared to DEC-205 or CD11c targeted NP.
2404 25068703 Moreover, subcutaneous vaccination with CD40, DEC-205 and CD11c-targeted NP consistently showed higher efficacy than non-targeted NP in stimulating CD8+ T cell responses.
2405 25068703 Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8(+) T cell response: a comparative study.
2406 25068703 These cell-surface molecules, including CD40, a TNF-α family receptor, DEC-205, a C-type lectin receptor and CD11c, an integrin receptor, were targeted by means of specific monoclonal antibodies (mAbs) coupled to the NP.
2407 25068703 We observed a small but significantly improved internalization of CD40-targeted NP compared to DEC-205 or CD11c targeted NP.
2408 25068703 Moreover, subcutaneous vaccination with CD40, DEC-205 and CD11c-targeted NP consistently showed higher efficacy than non-targeted NP in stimulating CD8+ T cell responses.
2409 25068703 Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8(+) T cell response: a comparative study.
2410 25068703 These cell-surface molecules, including CD40, a TNF-α family receptor, DEC-205, a C-type lectin receptor and CD11c, an integrin receptor, were targeted by means of specific monoclonal antibodies (mAbs) coupled to the NP.
2411 25068703 We observed a small but significantly improved internalization of CD40-targeted NP compared to DEC-205 or CD11c targeted NP.
2412 25068703 Moreover, subcutaneous vaccination with CD40, DEC-205 and CD11c-targeted NP consistently showed higher efficacy than non-targeted NP in stimulating CD8+ T cell responses.
2413 25117071 The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily.
2414 25117071 The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40.
2415 25117071 The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation.
2416 25117071 CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-κB (NF-κB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer.
2417 25117071 CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis.
2418 25117071 The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily.
2419 25117071 The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40.
2420 25117071 The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation.
2421 25117071 CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-κB (NF-κB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer.
2422 25117071 CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis.
2423 25117071 The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily.
2424 25117071 The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40.
2425 25117071 The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation.
2426 25117071 CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-κB (NF-κB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer.
2427 25117071 CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis.
2428 25130456 We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86.
2429 25131731 Lunasin-treated conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86, CD40) but also exhibited up-regulation of cytokines (IL1B, IL6) and chemokines (CCL3, CCL4).
2430 25136640 After IFN-γ-stimulation, ovalbumin- (OVA, 1 mg/mL) or OVA323-339 peptide-(0.5 μg/mL) treated SMCs failed to induce OT-II CD4(+) T cell activation/proliferation; this was also accompanied by a lack of expression of key costimulatory molecules (OX40L, CD40, CD70, and CD86) on SMCs.
2431 25162725 Localised productive infection triggered a broad innate response, with type-1 interferon sensitive IRF-7, STAT-1, TRIM5α and ApoBEC3G genes all upregulated during the acute phase but induction did not prevent viral persistence.
2432 25162725 Profound changes in vaccine-induced cell-surface markers of immune activation were detected on macrophages, B-cells and dendritic cells (DC-SIGN, S-100, CD40, CD11c, CD123 and CD86).
2433 25162725 Notably, high DC-SIGN and S100 staining for follicular and interdigitating DCs respectively, in MLN and spleen were detected by 3 days, persisting 20 weeks post-vaccination.
2434 25166494 Agonistic CD40 stimulation during CD8+ T cell priming in response to VSV infection enabled the resultant memory CD8+ T cell population to provide strong protective immunity against secondary infection.
2435 25166494 Our data suggest that immunomodulation of CD40 signaling may be a key adjuvant to enhance CD8+ T cell response during development of VSV vaccine strategies.
2436 25166494 Agonistic CD40 stimulation during CD8+ T cell priming in response to VSV infection enabled the resultant memory CD8+ T cell population to provide strong protective immunity against secondary infection.
2437 25166494 Our data suggest that immunomodulation of CD40 signaling may be a key adjuvant to enhance CD8+ T cell response during development of VSV vaccine strategies.
2438 25215306 X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways.
2439 25225119 We found that CTS downregulated the numbers of phagosomes inside the BMDCs, up-regulated the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs, decreased activity of ACP and phagocytosis by BMDCs, and induced production of higher levels of IL-12 and TNF-α.
2440 25229656 NK cells in the presence of HPV-VLPs enhanced DC-maturation as shown by an upregulation of CD86 and HLA-DR and an increased production of IL-12p70, but not of the immunosuppressive cytokine IL-10.
2441 25229656 This crosstalk between NK cells and DCs needed CD40 interaction and IL-12p70 secretion, whereas NKG2D was not implicated.
2442 25360749 DC treatment with EV71 VLPs enhanced the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR on the cell surface; increased the production of interleukin (IL)-12 p40, IL-12 p70, and IL-10 by DCs; and suppressed the capacity of DCs for endocytosis.
2443 25360749 Neutralization with antibodies against Toll-like receptor (TLR) 4 suppressed the capacity of EV71 VLPs to induce the production of IL-12 p40, IL-12 p70, and IL-10 by DCs and inhibited EV71 VLPs binding to DCs.
2444 25449707 Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is a crucial docking molecule for TNFR superfamily and Interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily.
2445 25454862 Further analysis proved that co-stimulatory molecules (CD40, CD80, CD86 and MHC-II), regulatory protein (IRF-7 and TRAF-6) and pro-inflammatory cytokines (IL-1, IL-6 and IL-12) were all changed and involved in DCs maturation.
2446 25457983 In the present study, Poly I:C (PIC, a TLR3 agonist), STAT3 siRNA and OVA antigen were co-encapsulated by poly (ethylene glycol)-b-poly (L-lysine)-b-poly (L-leucine) (PEG-PLL-PLLeu) polypeptide micelles to generate PMP/OVA/siRNA nanovaccine, which was aimed to effectively overcome DC dysfunction in vivo by deleting STAT3 gene in situ.
2447 25457983 PMP/OVA/siRNA also elevated CD86 and CD40 expression as well as IL-12 production by TADCs more effectively than PMP/OVA did, indicating its strong potency of inducing TADC maturation and activation.
2448 25465442 To overcome this, we studied vaccine delivery to DC via CD40-targeting using a multi-compound particulate vaccine with the aim to induce potent CD8(+) T cell responses.
2449 25465442 Targeting NP to CD40 led to very efficient and selective delivery to DC in vivo upon s.c. injection and improved priming of CD8(+) T cells against two independent tumor associated Ag.
2450 25465442 To overcome this, we studied vaccine delivery to DC via CD40-targeting using a multi-compound particulate vaccine with the aim to induce potent CD8(+) T cell responses.
2451 25465442 Targeting NP to CD40 led to very efficient and selective delivery to DC in vivo upon s.c. injection and improved priming of CD8(+) T cells against two independent tumor associated Ag.
2452 25466267 In vitro, the MP-based vaccine significantly increased dendritic cell (DC) activation with up-regulated CD40 and CD80 expression and IL-12 production compared to alum-based vaccine.
2453 25466267 Moreover, subcutaneous and intramuscular immunizations with MP-based vaccine augmented Granzyme B, Th1-type cytokines (IL-2, IL-12, and IFN-γ), and Th2 cytokine IL-4 secretions.
2454 25479725 In the presence of 17β-estradiol, DCs from aged rats exhibited an impaired ability to mature upon stimulation with LPS, as shown by the lower surface density of MHC II and costimulatory CD80 and CD86 molecules. 17β-Estradiol alone enhanced CD40 expression in OX62+ DCs without affecting the expression of other costimulatory molecules, thereby confirming that the expression of this molecule is regulated independently from the regulation of other costimulatory molecules.
2455 25479725 However, although R848 upregulated the expression of MHC II and CD80 and CD40 costimulatory molecules on DCs, 17β-estradiol diminished the effect of this TLR agonist only on MHC II expression.
2456 25479725 In the presence of 17β-estradiol, DCs from aged rats exhibited an impaired ability to mature upon stimulation with LPS, as shown by the lower surface density of MHC II and costimulatory CD80 and CD86 molecules. 17β-Estradiol alone enhanced CD40 expression in OX62+ DCs without affecting the expression of other costimulatory molecules, thereby confirming that the expression of this molecule is regulated independently from the regulation of other costimulatory molecules.
2457 25479725 However, although R848 upregulated the expression of MHC II and CD80 and CD40 costimulatory molecules on DCs, 17β-estradiol diminished the effect of this TLR agonist only on MHC II expression.
2458 25536061 Furthermore, LT-IIb and LT-IIc enhanced the total number of dendritic cells (DC) in the draining lymph node (DLN) and expression of costimulatory molecules CD80, CD86, and CD40 on DCs.
2459 25536171 B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.
2460 25536171 Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS).
2461 25536171 Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety.
2462 25536171 In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand.
2463 25536171 In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression.
2464 25536171 The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154.
2465 25536171 Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154.
2466 25536171 Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.
2467 25536171 B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.
2468 25536171 Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS).
2469 25536171 Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety.
2470 25536171 In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand.
2471 25536171 In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression.
2472 25536171 The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154.
2473 25536171 Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154.
2474 25536171 Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.
2475 25536171 B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.
2476 25536171 Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS).
2477 25536171 Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety.
2478 25536171 In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand.
2479 25536171 In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression.
2480 25536171 The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154.
2481 25536171 Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154.
2482 25536171 Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.
2483 25536171 B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.
2484 25536171 Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS).
2485 25536171 Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety.
2486 25536171 In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand.
2487 25536171 In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression.
2488 25536171 The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154.
2489 25536171 Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154.
2490 25536171 Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing effective T-independent antibody responses to microbial pathogens, allergens and vaccines.
2491 25566261 We report that Vγ9Vδ2 T cells induced expression of CD86, HLA-DR, and CD40 by B cells and stimulated the release of IL-4, IL-6, TNF-α, and IgG, IgA, and IgM.
2492 25566261 In contrast, Vγ9Vδ2 T cells induced expression of CD86 and HLA-DR and the release of IFN-γ, IL-6, and TNF-α by DC and these DC stimulated proliferation and IFN-γ production by conventional T cells.
2493 25622186 The functional maturation of BMDCs was confirmed by cytochemistry assay, FITC-dextran, acid phosphatase (ACP) activity, bio-assay and enzyme linked immunosorbent assay (ELISA).We elucidated that IL-2 up-regulated the expression of key surface markers such as: CD80, CD83, CD86, CD40 and MHC II molecules on BMDCs, down-regulated phagocytosis activity, induced more production of IL-12 and TNF-α secreted by BMDCs.
2494 25646303 In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8(+) T cells in the liver, and protective immunity induced by immunization with the Plasmodium yoelii fabb/f(-) genetically attenuated parasite.
2495 25646303 Using mixed adoptive transfers of polyclonal wild-type and CD40-deficient CD8(+) T cells into wild-type and CD40-deficient hosts, we evaluated the contributions to CD8(+) T cell immunity of CD40 expressed on host tissues including APC, compared with CD40 expressed on the CD8(+) T cells themselves.
2496 25646303 Most of the effects of CD40 could be accounted for by expression in the T cells' environment, including the accumulation of large numbers of CD8(+) T cells in the livers of immunized mice.
2497 25646303 In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8(+) T cells in the liver, and protective immunity induced by immunization with the Plasmodium yoelii fabb/f(-) genetically attenuated parasite.
2498 25646303 Using mixed adoptive transfers of polyclonal wild-type and CD40-deficient CD8(+) T cells into wild-type and CD40-deficient hosts, we evaluated the contributions to CD8(+) T cell immunity of CD40 expressed on host tissues including APC, compared with CD40 expressed on the CD8(+) T cells themselves.
2499 25646303 Most of the effects of CD40 could be accounted for by expression in the T cells' environment, including the accumulation of large numbers of CD8(+) T cells in the livers of immunized mice.
2500 25646303 In a mouse model of immunity to liver stage Plasmodium infection, CD40 was critical for the full maturation of liver dendritic cells, accumulation of CD8(+) T cells in the liver, and protective immunity induced by immunization with the Plasmodium yoelii fabb/f(-) genetically attenuated parasite.
2501 25646303 Using mixed adoptive transfers of polyclonal wild-type and CD40-deficient CD8(+) T cells into wild-type and CD40-deficient hosts, we evaluated the contributions to CD8(+) T cell immunity of CD40 expressed on host tissues including APC, compared with CD40 expressed on the CD8(+) T cells themselves.
2502 25646303 Most of the effects of CD40 could be accounted for by expression in the T cells' environment, including the accumulation of large numbers of CD8(+) T cells in the livers of immunized mice.
2503 25653426 Next, we analyzed parameters of DEC205 (CD205), Clec9A, CD11c, CD11b, and CD40 endocytosis and obtained quantitative measurements of internalization speed, surface turnover, and delivered Ag load.
2504 25653426 In contrast, targeting Ag to CD8(+) or CD8(-) DCs enhanced MHC I or MHC II Ag presentation, respectively.
2505 25698486 We found that delivery of rPmp18D with VCG was more effective than with CpG+FL in up-regulating the expression of molecules critically involved in T cell activation and differentiation, including MHC II, CD40, CD80, and CD86, activation of TLRs and NLRP3 inflammasome engagement, and secretion of IL-1β and TNF-α but not IL-10 and IL-4. rVCG-Pmp18D-immunized mice elicited more robust antigen-specific IFN-γ, IgA and IgG2c antibody responses compared to CpG+FL-delivered rPmp18D.
2506 25699040 This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and other molecules.
2507 25699040 Tfh cells are characterized by their expression of the chemokine receptor CXCR5, expression of the transcriptional repressor Bcl6, and their capacity to migrate to the follicle and promote germinal center B cell responses.
2508 25717328 Generation of Human B-Cell Lines Dependent on CD40-Ligation and Interleukin-4.
2509 25728020 This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7.
2510 25728020 PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells.
2511 25748337 Upon PFWE treatment, BM-DCs dose-dependently upregulated the expression of CD40, CD80, CD86 and MHC II and increased the production of IL-12, IL-6 and tumor necrosis factor (TNF)-α but not for IL-10, which is mediated by TLR4 signaling pathway, at least partially.
2512 25772201 It has been reported that glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and its ligand (GITRL) are involved in modulating both innate and adaptive immune responses.
2513 25772201 However, significantly higher levels of CD4(+)Th1, Th2 and CD8(+)IFN-γ(+)T cells were found in the pIRES/VP1/mGITRL group compared with control groups.
2514 25775390 Furthermore, sRCPS increased the levels of IL-4, IL-2, and IFN-γ in CD4(+)T cells and the level of IFN-γ in CD8(+)T cells.
2515 25775390 In addition, sRCPS enhanced the expression of CD40(+), CD80(+), CD86(+), MHC I and MHC II in dendritic cells (DCs) and upregulated the mRNA levels of MHC I, MHC II. sRCPS downregulated the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells. sRCPS increased both cellular and humoral immune responses by upregulating DC maturation, and suppressing the frequency of Treg cells.
2516 25780036 CD4+ T cell-derived IL-21 and deprivation of CD40 signaling favor the in vivo development of granzyme B-expressing regulatory B cells in HIV patients.
2517 25780036 In this article, we demonstrate that untreated HIV patients display CD4(+) T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B.
2518 25780036 Granzyme B-expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10.
2519 25780036 Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L.
2520 25780036 When culturing such IL-21(+)CD40L(-) Th cells with B cells, the former directly induce B cell differentiation into GraB cells.
2521 25780036 In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21-dependent B cell differentiation.
2522 25825910 Mixed lymphocyte reaction showed all Am-, Cp- and [Am+Cp]-treated DCs enhanced mouse CD4+ and CD8+ T-cell proliferation.
2523 25825910 Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs.
2524 25840621 Immunogenicity and protective efficacy of an Eimeria vaccine candidate based on Eimeria tenella immune mapped protein 1 and chicken CD40 ligand.
2525 25840621 The CD40 ligand (CD40L) has shown potential as a powerful immunological adjuvant in various studies.
2526 25840621 Immunogenicity and protective efficacy of an Eimeria vaccine candidate based on Eimeria tenella immune mapped protein 1 and chicken CD40 ligand.
2527 25840621 The CD40 ligand (CD40L) has shown potential as a powerful immunological adjuvant in various studies.
2528 25869965 Furthermore, NPs co-loaded with ovalbumin (OVA) and a molecular adjuvant, monophosphoryl lipid A (MPLA) promoted BMDC maturation and upregulation of co-stimulatory markers, including CD40, CD86, and MHC-II, and C57BL/6 mice vaccinated with NPs via intranasal route generated robust OVA-specific CD8(+) T cell and antibody responses.
2529 25888530 A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40.
2530 25934108 Moreover, CVPS increased the expression of IL-2, IFN-γ, and IL-4 in CD4(+) T cells and IFN-γ expression in CD8(+) T cells.
2531 25934108 Additionally, CVPS enhanced CD40(+), CD80(+), and CD86(+) expression on DCs.
2532 25934108 In contrast, CVPS downregulated TGF-β mRNA expression and the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells.
2533 25934108 Taken together, these results indicate that administering CVPS as an adjuvant enhances both cellular and humoral immune responses via the TLR-2 and TLR-4 signalling pathways, thereby promoting DC maturation and suppressing TGF-β expression and Treg frequency.
2534 25983089 Enhanced protective immunity derived from dendritic cells with phagocytosis of CD40 ligand transgene-engineered apoptotic tumor cells via increased dendritic cell maturation.
2535 25993535 The expression of co-stimulatory molecules (CD40, CD80 and CD86) in FTH-DCs was similar to that of DCs.
2536 26065687 Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h).
2537 26084003 Further, the findings of the insufficient maturation (CD86), co-stimulation (CD40) and migration (CCR7) activities of DCs together with the inadequate activation of the HBsAg-specific Th cells by APCs were identified as part of the reason for the HBsAg hyporesponse in B10.S mice, which supports the hypothesis that measures aimed at promoting the maturation, co-stimulation or migration of APCs to enhance Th cell activation may be a useful strategy for the development of new hepatitis B vaccines.
2538 26144666 Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86.
2539 26151223 Here we characterized rhesus macaque MZ B cells, present in secondary lymphoid tissue but not peripheral blood, as CD19(+), CD20(+), CD21(hi), IgM(+), CD22(+), CD38(+), BTLA(+), CD40(+), CCR6(+) and BCL-2(+).
2540 26185420 Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%), CDK2NA (90%), TP53 (75%-90%), DPC4/SMAD4 (50%).
2541 26185420 Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing.
2542 26289530 Interestingly, XHL in conjunction with inactivated FMD vaccine activated strong Th1 and Tc1 cell responses, especially Tfh cell responses, in immunized mice.
2543 26289530 XHL stimulated dendritic cell maturation by upregulating expression of major histocompatibility complex II (MHCII) molecules and co-stimulatory molecules CD40 and CD86 in immunized mice.
2544 26297758 Vaccination Produces CD4 T Cells with a Novel CD154-CD40-Dependent Cytolytic Mechanism.
2545 26297758 We demonstrate that immunization with a recombinant protein Ag and GLA-SE also induces granzyme A expression in CD4 T cells and produces cytolytic cells that can be detected in vivo.
2546 26297758 Surprisingly, these in vivo CTLs were CD4 T cells, not CD8 T cells, and this cytolytic activity was not dependent on granzyme A/B or perforin.
2547 26297758 Unlike previously reported CD4 CTLs, the transcription factors Tbet and Eomes were not necessary for their development.
2548 26297758 CTL activity was also independent of the Fas ligand-Fas, TRAIL-DR5, and canonical death pathways, indicating a novel mechanism of CTL activity.
2549 26297758 Rather, the in vivo CD4 CTL activity induced by vaccination required T cell expression of CD154 (CD40L) and target cell expression of CD40.
2550 26297758 Thus, vaccination with a TLR4 agonist adjuvant induces CD4 CTLs, which kill through a previously unknown CD154-dependent mechanism.
2551 26344742 Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP.
2552 26344742 We have recently reported that intramuscular injection of PCEP induces NLRP3, an inflammasome receptor gene, and inflammatory cytokines, including IL-1β and IL-18, in mouse muscle tissue.
2553 26344742 Caspase-1 is required for the processing of pro-forms of IL-1β and IL-18 into mature forms and is a critical constituent of the NLRP3 inflammasome.
2554 26344742 Hence, in the present study, we investigated the role of caspase-1 in the secretion of IL-1β and IL-18 in PCEP-stimulated splenic dendritic cells (DCs).
2555 26344742 Caspase inhibitor YVAD-fmk-treated splenic DCs showed significantly reduced IL-1β and IL-18 secretion in response to PCEP stimulation.
2556 26344742 Further, PCEP had no effect on the expression of MHC class II or co-stimulatory molecules, CD86 and CD40, suggesting that PCEP does not induce DC maturation.
2557 26405571 In an attempt to further improve the therapeutic responses, we treated 15 patients with melanoma, with autologous monocyte-derived immature DC electroporated with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively active TLR4 (caTLR4) together with mRNA encoding a tumor-associated antigen (TAA; respectively gp100 or tyrosinase).
2558 26405571 In conclusion, autologous mRNA-optimized DC can be safely administered intranodally to patients with metastatic melanoma but showed limited immunological responses against tyrosinase and gp100.
2559 26441965 Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella Infection.
2560 26441965 Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues.
2561 26441965 In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-γ and have elevated IL-10.
2562 26441965 A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where OT-II T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs.
2563 26441965 By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-γ that was lower than WT or CD40(-/-) DCs.
2564 26441965 DKO DCs pulsed with HKSOVA, but not with OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs.
2565 26441965 Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-γ or IL-10.
2566 26441965 However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (OT-II proliferation and IFN-γ production) DC functions and depend on the complexity of the antigen.
2567 26441965 Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella Infection.
2568 26441965 Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues.
2569 26441965 In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-γ and have elevated IL-10.
2570 26441965 A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where OT-II T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs.
2571 26441965 By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-γ that was lower than WT or CD40(-/-) DCs.
2572 26441965 DKO DCs pulsed with HKSOVA, but not with OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs.
2573 26441965 Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-γ or IL-10.
2574 26441965 However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (OT-II proliferation and IFN-γ production) DC functions and depend on the complexity of the antigen.
2575 26441965 Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella Infection.
2576 26441965 Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues.
2577 26441965 In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-γ and have elevated IL-10.
2578 26441965 A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where OT-II T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs.
2579 26441965 By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-γ that was lower than WT or CD40(-/-) DCs.
2580 26441965 DKO DCs pulsed with HKSOVA, but not with OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs.
2581 26441965 Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-γ or IL-10.
2582 26441965 However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (OT-II proliferation and IFN-γ production) DC functions and depend on the complexity of the antigen.
2583 26441965 Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella Infection.
2584 26441965 Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues.
2585 26441965 In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-γ and have elevated IL-10.
2586 26441965 A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where OT-II T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs.
2587 26441965 By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-γ that was lower than WT or CD40(-/-) DCs.
2588 26441965 DKO DCs pulsed with HKSOVA, but not with OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs.
2589 26441965 Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-γ or IL-10.
2590 26441965 However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (OT-II proliferation and IFN-γ production) DC functions and depend on the complexity of the antigen.
2591 26441965 Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella Infection.
2592 26441965 Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues.
2593 26441965 In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-γ and have elevated IL-10.
2594 26441965 A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where OT-II T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs.
2595 26441965 By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-γ that was lower than WT or CD40(-/-) DCs.
2596 26441965 DKO DCs pulsed with HKSOVA, but not with OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs.
2597 26441965 Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-γ or IL-10.
2598 26441965 However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (OT-II proliferation and IFN-γ production) DC functions and depend on the complexity of the antigen.
2599 26441965 Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella Infection.
2600 26441965 Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues.
2601 26441965 In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-γ and have elevated IL-10.
2602 26441965 A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where OT-II T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs.
2603 26441965 By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-γ that was lower than WT or CD40(-/-) DCs.
2604 26441965 DKO DCs pulsed with HKSOVA, but not with OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs.
2605 26441965 Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-γ or IL-10.
2606 26441965 However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (OT-II proliferation and IFN-γ production) DC functions and depend on the complexity of the antigen.
2607 26441965 Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella Infection.
2608 26441965 Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues.
2609 26441965 In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-γ and have elevated IL-10.
2610 26441965 A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where OT-II T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs.
2611 26441965 By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-γ that was lower than WT or CD40(-/-) DCs.
2612 26441965 DKO DCs pulsed with HKSOVA, but not with OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs.
2613 26441965 Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-γ or IL-10.
2614 26441965 However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (OT-II proliferation and IFN-γ production) DC functions and depend on the complexity of the antigen.
2615 26465323 Specifically, Th1-specific cytokines (IFN-γ, IL-2, TNF-α), CD40 ligand and the Th1 lineage-specifying transcription factor Tbet were determined upon stimulation with peptides covering the TBEV structural proteins contained in the vaccine (C-capsid, prM/M-membrane and E-envelope).