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Gene Information

Gene symbol: APC

Gene name: adenomatous polyposis coli

HGNC ID: 583

Synonyms: DP2, DP3, DP2.5, PPP1R46

Related Genes

# Gene Symbol Number of hits
1 ANKRD36B 1 hits
2 CCL3 1 hits
3 CCL5 1 hits
4 CD14 1 hits
5 CD1A 1 hits
6 CD1D 1 hits
7 CD2 1 hits
8 CD207 1 hits
9 CD209 1 hits
10 CD28 1 hits
11 CD3G 1 hits
12 CD4 1 hits
13 CD40 1 hits
14 CD40LG 1 hits
15 CD58 1 hits
16 CD68 1 hits
17 CD69 1 hits
18 CD80 1 hits
19 CD83 1 hits
20 CD86 1 hits
21 CD8A 1 hits
22 CEACAM5 1 hits
23 CLEC7A 1 hits
24 CSF2 1 hits
25 CTAG1B 1 hits
26 CTLA4 1 hits
27 CTNNB1 1 hits
28 CYCS 1 hits
29 ERBB2 1 hits
30 F2 1 hits
31 F2R 1 hits
32 FASLG 1 hits
33 GAST 1 hits
34 GPI 1 hits
35 HLA-A 1 hits
36 HSPA1A 1 hits
37 HSPH1 1 hits
38 ICAM1 1 hits
39 ICOSLG 1 hits
40 IFNG 1 hits
41 IL10 1 hits
42 IL12A 1 hits
43 IL13 1 hits
44 IL1B 1 hits
45 IL2 1 hits
46 IL2RA 1 hits
47 IL4 1 hits
48 IL6 1 hits
49 IL7 1 hits
50 ITGAL 1 hits
51 ITGAM 1 hits
52 ITGAX 1 hits
53 JAG1 1 hits
54 JUP 1 hits
55 LAMP3 1 hits
56 LBR 1 hits
57 LRP1 1 hits
58 MAGEA1 1 hits
59 MARK2 1 hits
60 MIA 1 hits
61 MLANA 1 hits
62 MMP9 1 hits
63 MRC1 1 hits
64 MSC 1 hits
65 MUC1 1 hits
66 NOS2A 1 hits
67 PLAG1 1 hits
68 PLP1 1 hits
69 PROCR 1 hits
70 PSMB10 1 hits
71 PSMB8 1 hits
72 PTGS2 1 hits
73 REEP5 1 hits
74 SIRPA 1 hits
75 TAP1 1 hits
76 TGFA 1 hits
77 TH1L 1 hits
78 THBD 1 hits
79 TLR1 1 hits
80 TLR2 1 hits
81 TLR4 1 hits
82 TNF 1 hits
83 TNFAIP3 1 hits
84 TP53 1 hits

Related Sentences

# PMID Sentence
1 1379185 Here we show that infection of B cell lines as APC with viruses of two different families, namely, influenza A or vaccinia, completely block processing and presentation of an exogenous globular protein antigen pigeon cytochrome c.
2 1379185 Only live infectious virus, not UV-inactivated virus blocks APC function, indicating that there is no competition of viral particles with cytochrome c for the class II processing machinery.
3 1379185 Here we show that infection of B cell lines as APC with viruses of two different families, namely, influenza A or vaccinia, completely block processing and presentation of an exogenous globular protein antigen pigeon cytochrome c.
4 1379185 Only live infectious virus, not UV-inactivated virus blocks APC function, indicating that there is no competition of viral particles with cytochrome c for the class II processing machinery.
5 1834737 Characterization of streptococcal antigen-specific CD8+, MHC class I-restricted, T cell clones that down-regulate in vitro antibody synthesis.
6 1834737 The function of the CD8+ cloned cells was examined in vitro for their effect on antibody synthesis by Ag-stimulated CD4+ cells and B cells from immunized animals.
7 1834737 Indeed, four of the five clones suppressed SAI/II-specific IgG antibody synthesis when activated with SAI/II and the appropriate MHC-matched APC.
8 7499830 Glycosylphosphatidylinositol (GPI)-modified variants of murine B7-1 and B7-2 cell surface costimulators were produced via chimerization with alternative GPI-modification signal sequences from decay-accelerating factor (DAF).
9 7499830 GPI anchorage was verified by demonstrating phosphatidylinositol-specific phospholipase C (PI-PLC) sensitivity of the chimeric polypeptides in both immunofluorescence/flow-cytometric and immunoprecipitation analyses.
10 7499830 The various GPI-modified chimeric B7-1:DAF and B7-2:DAF polypeptides were shown to retain costimulator function, in both an in vitro proliferation assay and an in vivo triggering of cytotoxicity assay.
11 7499830 Moreover, the functionality of the GPI-modified variants in enhancing the immunogenicity of the murine T lymphoma line EL-4 suggests a novel route for generating APC-centered immunotherapeutics, including cellular cancer vaccines, that is based upon protein transfer of GPI-modified costimulators.
12 7533857 To increase the inherently weak immunogenicity of synthetic peptide vaccines, we used recombinant DNA techniques to generate chimeras between immunogenic determinants of human immunodeficiency virus type 1 (HIV-1) gp120 and antibody Fab fragments reactive with surface structures displayed specifically on human antigen-presenting cells (APCs), including surface immunoglobulin D (sIgD) and class II major histocompatibility complex (MHC) molecules.
13 7533857 Furthermore, such recombinant immunotargeted HIV-1 peptide antigens demonstrated improved immunogenicity over equivalent nonimmunotargeted control antigens, as shown by their ability to stimulate interleukin-2 production by CD4+ T-helper cells from human donors exposed to HIV-1 antigens.
14 7533857 These data suggest that immunotargeting of recombinant peptide antigens via the attached Fab fragments facilitates uptake by human APCs with subsequent access to the MHC class II processing pathway, thereby validating the immunotargeting concept for such recombinant subunit vaccines in an in vitro human system.
15 7533857 To increase the inherently weak immunogenicity of synthetic peptide vaccines, we used recombinant DNA techniques to generate chimeras between immunogenic determinants of human immunodeficiency virus type 1 (HIV-1) gp120 and antibody Fab fragments reactive with surface structures displayed specifically on human antigen-presenting cells (APCs), including surface immunoglobulin D (sIgD) and class II major histocompatibility complex (MHC) molecules.
16 7533857 Furthermore, such recombinant immunotargeted HIV-1 peptide antigens demonstrated improved immunogenicity over equivalent nonimmunotargeted control antigens, as shown by their ability to stimulate interleukin-2 production by CD4+ T-helper cells from human donors exposed to HIV-1 antigens.
17 7533857 These data suggest that immunotargeting of recombinant peptide antigens via the attached Fab fragments facilitates uptake by human APCs with subsequent access to the MHC class II processing pathway, thereby validating the immunotargeting concept for such recombinant subunit vaccines in an in vitro human system.
18 7636236 Because the env protein associates tightly with CD4 shortly after synthesis, we first targeted the env protein using a chimeric CD4 protein consisting of the extracellular domain of CD4 and the transmembrane and cytoplasmic domains of LAMP-1.
19 7636236 The enhanced stimulatory capacity of APC expressing LAMP-1-targeted Ags has important implications for vaccine design.
20 7901150 This is recognized by immune CD4 T cells which function as essential helper cells in the generation of the CD8 CTL response.
21 7901150 The existence of two types of cognate T cell responses in a syngeneic anti-tumour response was directly proved by the establishment of two types of tumour specific T cell lines which required as co-stimulator either MHC class II positive APC or IL-2.
22 7901150 The generation of the tumour specific CTL response could be blocked by monoclonal antibodies against all the molecules involved in the cognate interactions (i.e. class I MHC, CD8, class II MHC, CD4 and TCR) but not by anti-CD2 or anti-IgG.
23 7901150 The strict requirement for helper cells and APC could be bypassed by the addition of recombinant IL-2 but optimal triggering of CD8 CTL-precursor required viable tumour stimulator cells.
24 7901150 This well characterized in vitro assay may be useful (i) for monitoring the immune status of CD4 and CD8 immune T cells separately, for instance of tumour bearing and/or treated animals and (ii) for the development and testing of potent tumour cell vaccines with T cell stimulatory and/or co-stimulatory activities.
25 8361775 Antibody-dependent MIA titres were much lower than for APC-dependent MIA.
26 8732694 Effective immunization against neuroblastoma using double-transduced tumor cells secreting GM-CSF and interferon-gamma.
27 8732694 Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector MFG-granulocyte-macrophage colony-stimulating factor (GM-CSF), to examine immune stimulation conferred by localized GM-CSF production.
28 8732694 Because both CD4+ and CD8+ T cells were necessary during priming to this MHC class Ilo, II-tumor, these data indicate that major histocompatibility complex (MHC) class I+, II+ antigen-presenting cells (APCs) were required for the T-cell antitumor response.
29 8732694 Co-expression of GM-CSF and IFN-gamma, both of which have immunostimulatory activities on antigen-presenting cells, abrogated the tumorigenic potential of this tumor and increased immunogenicity over N-2a/IFN but not N-2a/GM.
30 9005958 To address this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T cell responses when tumor cells were infected with a single, recombinant, vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule.
31 9325017 To identify factors relevant to the unique property of iscoms to mediate CTL responses, we analysed the capacity of different defined Quillaja triterpenoid components in various formulations to stimulate production of IL-6 by APC in vitro and in vivo.
32 9548476 Heat-killed Sendai virus Ags were efficiently processed by normal B6 as well as by TAP-1(-/-) splenic APC.
33 9548476 Presentation was MHC class I restricted, since no presentation was seen by APC from TAP-1/beta2m-/- mice that lack expression of MHC class I.
34 9548476 Finally, B6 as well as TAP-1(-/-) splenic APC, loaded with heat-killed Sendai virus Ag in vitro, primed naive CD8+ T cells in vivo.
35 9548476 Heat-killed Sendai virus Ags were efficiently processed by normal B6 as well as by TAP-1(-/-) splenic APC.
36 9548476 Presentation was MHC class I restricted, since no presentation was seen by APC from TAP-1/beta2m-/- mice that lack expression of MHC class I.
37 9548476 Finally, B6 as well as TAP-1(-/-) splenic APC, loaded with heat-killed Sendai virus Ag in vitro, primed naive CD8+ T cells in vivo.
38 9548476 Heat-killed Sendai virus Ags were efficiently processed by normal B6 as well as by TAP-1(-/-) splenic APC.
39 9548476 Presentation was MHC class I restricted, since no presentation was seen by APC from TAP-1/beta2m-/- mice that lack expression of MHC class I.
40 9548476 Finally, B6 as well as TAP-1(-/-) splenic APC, loaded with heat-killed Sendai virus Ag in vitro, primed naive CD8+ T cells in vivo.
41 9550372 Immunostimulatory effects of a plasmid expressing CD40 ligand (CD154) on gene immunization.
42 9550372 Interaction of CD40 with its ligand (CD154) can induce CD40-bearing APCs to express immune stimulatory accessory molecules that facilitate immune recognition.
43 9554257 Further, iscoms induce APC to produce IL-1, IL-6 and IL-12 and a TH1 type of response with enhanced IL-2 and IFN-gamma production.
44 9626347 The generation of MUC1-specific CTLs required only a 6-day in vitro stimulation of patients' T-cells with synthetic MUC1-peptide-pulsed autologous APCs.
45 10092787 Proliferative responses and production of the Th1 cytokines, IL-2 and IFN-gamma, were reduced in T cells responsive to PLP139-151.
46 10092787 In the brains of mice that were successfully vaccinated, mRNA for IL-2, IL-15, and IFN-gamma were reduced.
47 10092787 DNA immunization with the myelin minigene for PLP-altered expression of B7.1 (CD80), and B7.2 (CD86) on APCs in the spleen.
48 10228040 These noncytolytic CD4+ T cells synthesize large quantities of type 2 cytokines such as IL-4 and IL-10 on stimulation with the autologous APC or tumor cells in an MHC class II-restricted manner.
49 10228040 The supernatant factor also exhibits a marked inhibitory effect on the expression of the costimulatory molecules, CD80 and CD86, by APC.
50 10607750 However, upon re-stimulation with fresh APC and antigen, tolerized T(h)1 cells failed to proliferate or to produce T(h)1 cytokine message or secreted protein, had decreased expression of CD25, CD28 and B7 and increased expression of MHC class II molecules, and demonstrated an enhanced commitment to apoptosis.
51 10640735 Interaction between B7 on APC and CD28 on naive T cells is necessary for priming the T cells.
52 10640735 On the other hand, interaction between B7 on APC and CTLA-4 on activated T cells transduces a negative regulatory signal to the activated T cells.
53 10640735 Interaction between B7 on APC and CD28 on naive T cells is necessary for priming the T cells.
54 10640735 On the other hand, interaction between B7 on APC and CTLA-4 on activated T cells transduces a negative regulatory signal to the activated T cells.
55 10770625 Enhanced antitumoral effect of adenovirus-mediated cytosine deaminase gene therapy by induction of antigen-presenting cells through stem cell factor/granulocyte-macrophage colony-stimulating factor gene transfer.
56 10770625 We preinjected the mice with murine stem cell factor (SCF)-encoding adenovirus (AdSCF) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-encoding adenovirus (AdGM-CSF); after 7 days, the mice were inoculated with CT26 colon adenocarcinoma.
57 10770625 Cytotoxic T-lymphocyte activity was induced efficiently after the combined therapy, and mRNA of tumor necrosis factor-alpha, interleukin-4, interferon-gamma, and interleukin-2 was present in the tumor mass after combined therapy, suggesting that a more potent antitumoral response was induced by enhanced APCs.
58 10915558 LFA-3 plasmid DNA enhances Ag-specific humoral- and cellular-mediated protective immunity against herpes simplex virus-2 in vivo: involvement of CD4+ T cells in protection.
59 10915558 Adhesion molecules lymphocyte function-associated antigen (LFA)-1 and CD2 on T cells recognize intercellular adhesion molecule (ICAM)-1 and LFA-3 on APCs, respectively.
60 10915558 To investigate specific roles of adhesion molecules in immune induction we coimmunized LFA-3 and ICAM-1 cDNAs with a gD plasmid vaccine and then analyzed immune modulatory effects and protection against lethal herpes simplex virus (HSV)-2 challenge.
61 10915558 LFA-3 also enhanced Th cell proliferative responses and production of interleukin (IL)-2, interferon-gamma, IL-4, and IL-10 from splenocytes.
62 10915558 In contrast, ICAM-1 showed slightly increasing effects on T-cell proliferation responses and cytokine production. beta-Chemokine production (RANTES, MIP-1alpha, and MCP-1) was also influenced by LFA-3 or ICAM-1.
63 10915558 When animals were challenged with a lethal dose of HSV-2, LFA-3-coimmunized animals exhibited an enhanced survival rate, as compared to animals given ICAM-1 or gD DNA vaccine alone.
64 10915558 These studies demonstrate that adhesion molecule LFA-3 can play an important role in generating protective antigen-specific immunity in the HSV model system through increased induction of CD4+ Th1 T-cell subset.
65 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.
66 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.
67 11043379 Triggering of CD40 with antibodies in vivo can replace the need for CD40L-expressing CD4+ T helper cells for cross-priming of CTL.
68 11043379 Interestingly, differential involvement of CD40/CD40L in immune responses can be observed between various immunological sites in the body.
69 11050151 Regulation of beta -catenin transformation by the p300 transcriptional coactivator.
70 11050151 The beta-catenin protein plays a critical role in embryonic development and mature tissue homeostasis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction.
71 11050151 In colon and other cancers, mutations of beta-catenin or the adenomatous polyposis coli (APC) tumor suppressor appear to stabilize beta-catenin and enhance its interaction with T cell factor (TCF) or lymphoid enhancer factor (Lef) transcription factors.
72 11050151 At present, a complete picture of the means by which beta-catenin's interactions with TCF/Lef proteins contribute to neoplastic transformation is lacking.
73 11050151 We report that the transcriptional coactivator p300 interacts with beta-catenin in vitro and in vivo and is critical for beta-catenin-mediated neoplastic transformation. p300 synergistically activates beta-catenin/TCF transcription, and their biochemical association requires the CH1 domain of p300 and a region of beta-catenin that includes its NH(2)-terminal transactivation domain and the first two armadillo repeats.
74 11050151 Lowering of cellular p300 levels by using a ribozyme directed against p300 reduced TCF transcriptional activity and inhibited the neoplastic growth properties of a beta-catenin-transformed rat epithelial cell line and a human colon carcinoma line with a beta-catenin mutation.
75 11050151 These findings demonstrate a critical role for p300 in beta-catenin/TCF transcription and in cancers arising from defects in beta-catenin regulation.
76 11123322 This study represents the first time CD8(+) T cells generated against Mtb-infected APC have been used to elucidate an Mtb-specific CD8(+) T cell Ag.
77 11212260 Some colorectal adenomas express cholecystokinin B/gastrin receptor mRNA, and thus hypergastrinemia may increase progression through the adenoma-carcinoma sequence.
78 11212260 Serum gastrin levels in APC(Min-/+) mice were elevated 5-6-fold by oral administration of omeprazole (75 mg/kg).
79 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.
80 11223075 Furthermore, cytotoxic responses to tumours may fail because the Th-cell response is inadequate and unable to provide CD40 stimulation of APC.
81 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).
82 11223075 In addition, depletion of CD8(+) cells abrogated protection whilst depletion of CD4(+) cells had no effect.
83 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.
84 11223075 Furthermore, cytotoxic responses to tumours may fail because the Th-cell response is inadequate and unable to provide CD40 stimulation of APC.
85 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).
86 11223075 In addition, depletion of CD8(+) cells abrogated protection whilst depletion of CD4(+) cells had no effect.
87 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.
88 11223075 Furthermore, cytotoxic responses to tumours may fail because the Th-cell response is inadequate and unable to provide CD40 stimulation of APC.
89 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).
90 11223075 In addition, depletion of CD8(+) cells abrogated protection whilst depletion of CD4(+) cells had no effect.
91 11251876 Both LT and CT induce B7-2 expression on antigen-presenting cells (APCs) for subsequent co-stimulatory signalling to CD4+ T cells.
92 11251876 CT directly affects CD4+ T cells activated via the TCR-CD3 complex with selective inhibition of Th1 responses whereas LT maintains Th1 cytokine responses with inhibition of interleukin (IL)-4 production.
93 11251876 Nontoxic mutant (m)CTs (S61F and E112K) retain adjuvant properties by inducing CD4+ Th2 cells, which provided effective help for the Ag-specific mucosal immunoglobulin (Ig)A, as well as serum IgG1, IgE and IgA Ab responses.
94 11251876 Firstly, mCT enhanced the B7-2 expression of APCs.
95 11251876 Both LT and CT induce B7-2 expression on antigen-presenting cells (APCs) for subsequent co-stimulatory signalling to CD4+ T cells.
96 11251876 CT directly affects CD4+ T cells activated via the TCR-CD3 complex with selective inhibition of Th1 responses whereas LT maintains Th1 cytokine responses with inhibition of interleukin (IL)-4 production.
97 11251876 Nontoxic mutant (m)CTs (S61F and E112K) retain adjuvant properties by inducing CD4+ Th2 cells, which provided effective help for the Ag-specific mucosal immunoglobulin (Ig)A, as well as serum IgG1, IgE and IgA Ab responses.
98 11251876 Firstly, mCT enhanced the B7-2 expression of APCs.
99 11517321 Targeting of antigens to antigen-presenting cells (APCs) increases CD4(+) T cell activation, and this observation can be exploited in the development of new vaccines.
100 11731437 A new murine model of human colorectal cancer was generated by crossing human carcinoembryonic antigen (CEA) transgenic mice (H-2K(b)) with adenomatous polyposis coli (Apc1638N) knockout mice (H-2K(b)).
101 11738738 Enhanced activation of rhesus T cells by vectors encoding a triad of costimulatory molecules (B7-1, ICAM-1, LFA-3).
102 11738738 Several molecules normally found on the surface of professional human APCs are capable of providing the second signals critical for T cell activation: B7-1 (CD80), ICAM-1 (CD54), and LFA-3 (CD58).
103 11738738 We have recently designed and characterized both recombinant vaccinia and recombinant avipox vectors containing the transgenes for a triad of human T cell costimulatory molecules (B7-1, ICAM-1, LFA-3; designated TRICOM).
104 12384803 Th1-type responses which comprise cell-mediated immunity are characterised by the secretion of interferon-gamma by T cells, which is induced by antigen-presenting cell (APC)-derived IL-12.
105 12460911 CEA.Tg mice were crossed with mice bearing a mutation in the Apc gene (MIN mice), and the CEA.Tg/MIN progeny developed multiple intestinal neoplasms, which overexpress CEA to levels that are reminiscent of those reported for tubulovillous intestinal adenomas from patients.
106 12460911 CEA.Tg/MIN mice were vaccinated with an aggressive diversified prime/boost vaccine regimen: (a) a primary vaccine consisting of recombinant vaccinia virus-expressing CEA and a triad of costimulatory molecules (TRICOM): B7.1, ICAM-1, and LFA-3 (rV-CEA-TRICOM); and (b) a booster vaccine using CEA-TRICOM in a recombinant avipox (fowlpox) virus (rF-CEA-TRICOM).
107 12517965 The objective of this study was to test the ability of bovine CD154 to target a plasmid-encoded Ag to CD40-expressing APCs.
108 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.
109 12517965 The chimeric tgD-CD154 was expressed in vitro in COS-7 cells and reacted with both glycoprotein D- and CD154-specific Abs.
110 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.
111 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.
112 12562324 APC from CD40 knockout mice were as effective as wild-type APC for the induction of non-specific and GXM-specific responses.
113 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.
114 12922111 Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation.
115 12922111 All three immunostimulants also elicited CD86-dependent TH1 cytokine responses.
116 14734740 Escherichia coli expressing recombinant antigen and listeriolysin O stimulate class I-restricted CD8+ T cells following uptake by human APC.
117 14734740 These results demonstrate that recombinant E. coli can be engineered to direct Ags to the cytosol of human phagocytic APCs, and suggest possible vaccine strategies for generating CD8(+) T cell responses against pathogens or tumors.
118 14734740 Escherichia coli expressing recombinant antigen and listeriolysin O stimulate class I-restricted CD8+ T cells following uptake by human APC.
119 14734740 These results demonstrate that recombinant E. coli can be engineered to direct Ags to the cytosol of human phagocytic APCs, and suggest possible vaccine strategies for generating CD8(+) T cell responses against pathogens or tumors.
120 15100266 Bacterial heat shock proteins promote CD91-dependent class I MHC cross-presentation of chaperoned peptide to CD8+ T cells by cytosolic mechanisms in dendritic cells versus vacuolar mechanisms in macrophages.
121 15100266 APCs process mammalian heat shock protein (HSP):peptide complexes to present HSP-chaperoned peptides on class I MHC (MHC-I) molecules to CD8(+) T cells.
122 15100266 HSP-enhanced MHC-I peptide presentation occurred only if peptide was complexed to the prokaryotic HSP and was dependent on CD91, establishing CD91 as a receptor for prokaryotic as well as mammalian HSPs.
123 15100266 Prokaryotic HSPs are a potential source of microbial peptide Ags during phagocytic processing of bacteria during infection and could potentially be incorporated in vaccines to enhance presentation of peptides to CD8(+) T cells.
124 15150127 The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli.
125 15150127 Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib.
126 15150127 When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2.
127 15150127 The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli.
128 15150127 Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib.
129 15150127 When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2.
130 15336780 Using tetramer staining and limiting dilution analyses as monitors of CTL responses, we found significant increases in the number of antigen-specific CTL in circulation after vaccination with the MART-1(27-35) peptide (AAGIGILTV)-pulsed autologous APC, the MAGE-1(161-169) peptide (EADPTGHSY)-pulsed APC, or with autologous tumor lysate-pulsed APC.
131 15336780 The decline in the CTL response was associated by a concomitant expansion of CD4(+) CD25(+)T cells.
132 15336780 Analysis of postvaccine peripheral blood lymphocytes (PBL) from patients showed an increased amount of interleukin (IL)-10 secretion on in vitro stimulation with IL-2 after successive vaccination.
133 15336780 Triple color flow cytometric analyses revealed cytoplasmic IL-10 in the CD4(+)CD25(+) T-cell fraction and the number of CD4(+)CD25(+) IL-10(+) T cells were found to increase significantly in postvaccine PBL.
134 15470057 APCs process heat shock protein (HSP):peptide complexes to present HSP-chaperoned peptides on class I MHC molecules, but the ability of HSPs to contribute chaperoned peptides for class II MHC (MHC-II) Ag processing and presentation is unclear.
135 15470057 Bacterial HSPs enhanced MHC-II presentation only if peptide was complexed to the HSP, suggesting that the key HSP function was enhanced delivery or processing of chaperoned peptide Ag rather than generalized enhancement of APC function.
136 15470057 Bacterial HSPs are a potential source of microbial peptide Ags during phagocytic processing of bacteria during infection and could potentially be incorporated in vaccines to enhance presentation of peptides to CD4+ T cells.
137 15470057 APCs process heat shock protein (HSP):peptide complexes to present HSP-chaperoned peptides on class I MHC molecules, but the ability of HSPs to contribute chaperoned peptides for class II MHC (MHC-II) Ag processing and presentation is unclear.
138 15470057 Bacterial HSPs enhanced MHC-II presentation only if peptide was complexed to the HSP, suggesting that the key HSP function was enhanced delivery or processing of chaperoned peptide Ag rather than generalized enhancement of APC function.
139 15470057 Bacterial HSPs are a potential source of microbial peptide Ags during phagocytic processing of bacteria during infection and could potentially be incorporated in vaccines to enhance presentation of peptides to CD4+ T cells.
140 15585869 APCs expressing the activation markers MHC class II, CD80, and CD40 increased in number in the lung.
141 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.
142 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.
143 15787741 Abstract Heat shock proteins (Hsp) can deliver antigen into the major histocompatibility complex class I presentation pathway of antigen-presenting cells (APC), a process called cross priming, thus stimulating antigen-specific CD8+ T-cell reactions.
144 15787741 Both processes require interaction of Hsp with APC via specific receptors.
145 15787741 This study describes the interaction of recombinant Hsp70 (rHsp70) of Mycobacterium avium subspecies paratuberculosis with bovine peripheral blood mononuclear cells that was restricted to CD14+ cells.
146 16178769 In particular, modulation of the expression of co-stimulatory molecules on the targeted APC; CD80, CD86, CD83 and B7RP-1, play important roles for the effect of the ADP-ribosylating CTA1-based adjuvants for the development of tolerance or active IgA immunity.
147 16186817 Recently activated, but not resting, CD4(+) T cells express CD154, providing costimulatory signals to B cells and antigen-presenting cells (APCs).
148 16186817 Therefore, de novo CD154 expression after stimulation identifies antigen-specific CD4(+) T cells.
149 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(+).
150 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.
151 16424054 In this study, we determine the ability of grp170 and its structural domains to (a) bind to and present melanoma-associated antigen gp100 to the immune system and (b) to bind to receptors on APCs.
152 16585571 Engagement of CD28 outside of the immunological synapse results in up-regulation of IL-2 mRNA stability but not IL-2 transcription.
153 16585571 During T cell activation by APC, CD28 is colocalized with TCR in the central supramolecular activation cluster (cSMAC) region of the immunological synapse.
154 16585571 CD28 signaling through PI3K results in the recruitment of protein kinase C (PKC)theta to the cSMAC, activation of NF-kappaB, and induction of IL-2 transcription.
155 16585571 To test this model we have examined the mechanism of CD28-mediated induction of IL-2 secretion when CD28 is engaged outside of the immunological synapse.
156 16585571 CD4 T cells were stimulated with Ag presented by B7-negative APC and CD28 costimulation was provided in trans by anti-CD28-coated beads or by class II-negative, B7-positive cells.
157 16585571 We show that induction of IL-2 secretion under these conditions did not require expression of PKCtheta and did not induce NF-kappaB activation or IL-2 transcription.
158 16585571 In contrast, CD28 costimulation in trans did induce IL-2 mRNA stability, accounting for the up-regulation of IL-2 secretion.
159 16585571 These data indicate that the ability of CD28 to up-regulate IL-2 transcription requires colocalization of TCR and CD28 at the plasma membrane, possibly within the cSMAC of the immunological synapse.
160 16585571 In contrast, the ability of CD28 to promote IL-2 mRNA stability can be transduced from a distal site from the TCR, suggesting that signal integration occurs downstream from the plasma membrane.
161 16585571 Engagement of CD28 outside of the immunological synapse results in up-regulation of IL-2 mRNA stability but not IL-2 transcription.
162 16585571 During T cell activation by APC, CD28 is colocalized with TCR in the central supramolecular activation cluster (cSMAC) region of the immunological synapse.
163 16585571 CD28 signaling through PI3K results in the recruitment of protein kinase C (PKC)theta to the cSMAC, activation of NF-kappaB, and induction of IL-2 transcription.
164 16585571 To test this model we have examined the mechanism of CD28-mediated induction of IL-2 secretion when CD28 is engaged outside of the immunological synapse.
165 16585571 CD4 T cells were stimulated with Ag presented by B7-negative APC and CD28 costimulation was provided in trans by anti-CD28-coated beads or by class II-negative, B7-positive cells.
166 16585571 We show that induction of IL-2 secretion under these conditions did not require expression of PKCtheta and did not induce NF-kappaB activation or IL-2 transcription.
167 16585571 In contrast, CD28 costimulation in trans did induce IL-2 mRNA stability, accounting for the up-regulation of IL-2 secretion.
168 16585571 These data indicate that the ability of CD28 to up-regulate IL-2 transcription requires colocalization of TCR and CD28 at the plasma membrane, possibly within the cSMAC of the immunological synapse.
169 16585571 In contrast, the ability of CD28 to promote IL-2 mRNA stability can be transduced from a distal site from the TCR, suggesting that signal integration occurs downstream from the plasma membrane.
170 16893998 Immunotargeting with CD154 (CD40 ligand) enhances DNA vaccine responses in ducks.
171 16893998 Engagement of CD154 on activated T cells with CD40 on antigen-presenting cells (APCs) potentiates adaptive immune responses in mammals.
172 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.
173 16942487 In this study, we developed a novel strategy for the APC to efficiently cross-present a fusion tumour antigen, which contains both MHC class I-restricted and class II-restricted T-cell epitopes from Her-2/neu and p53 in a cognate manner.
174 16942487 The N-terminus of the fusion Her-2/neu, p53 protein was linked to the sequence encoding for human secondary lymphoid-tissue chemokine for secretion and chemokinesis, and the C-terminus of the fusion protein was linked to a cell-binding domain of IgG (Fc portion, the cell-binding domain of IgG) for receptor-mediated internalization.
175 17339467 Listeria monocytogenes (Lm) targets the cytoplasm of APC and is a strong CD8 and CD4 Th1-promoting vaccine vehicle in adult mice.
176 17339467 We found that neonatal mice immunized only once with the attenuated strain DeltaactA-Lm developed robust primary and secondary CD8 and CD4 Th1 responses and were fully protected from lethal challenge with virulent wild-type Lm without the need for a booster immunization.
177 17339467 Furthermore, DeltaactA-Lm expressing a heterologous recombinant Ag induced a strong CD8 and Th1 memory response to that Ag.
178 17540847 Here we compare monomeric and dimeric forms of MIP-1alpha and RANTES that target Id to APCs in a mouse B lymphoma (A20) and a multiple myeloma model (MOPC315).
179 17540847 MIP-1alpha was more potent than RANTES.
180 17540847 When delivered in vivo by intramuscular injection of plasmids followed by electroporation, dimeric proteins efficiently primed APCs in draining lymph nodes for activation and proliferation of Id-specific CD4(+) T cells.
181 17540847 Here we compare monomeric and dimeric forms of MIP-1alpha and RANTES that target Id to APCs in a mouse B lymphoma (A20) and a multiple myeloma model (MOPC315).
182 17540847 MIP-1alpha was more potent than RANTES.
183 17540847 When delivered in vivo by intramuscular injection of plasmids followed by electroporation, dimeric proteins efficiently primed APCs in draining lymph nodes for activation and proliferation of Id-specific CD4(+) T cells.
184 17548590 To determine the mechanism by which the IFN-gamma-inducible proteasome (immuno) subunits enhance the ability of specific pathogen-derived peptides to elicit CD8 T cell responses, we generated a recombinant Listeria monocytogenes strain (rLM-E1) that secretes a model Ag encompassing the immunoproteasome-dependent E1B(192-200) and immunoproteasome-independent E1A(234-243) epitope.
185 17548590 Analyses of Ag presentation showed that infected gene-deficient professional APCs, lacking the immunosubunits LMP7/ibeta5 and MECL-1/ibeta2, processed and presented the rLM-E1-derived E1B(192-200) epitope but with delayed kinetics.
186 17548590 Accordingly, infected gene-deficient mice failed to respond to the otherwise immunodominant E1B(192-200) epitope but mounted normal CD8 T cell responses to E1A(234-243) which was processed by the same professional APCs, from the same rLM-E1 Ag.
187 17548590 To determine the mechanism by which the IFN-gamma-inducible proteasome (immuno) subunits enhance the ability of specific pathogen-derived peptides to elicit CD8 T cell responses, we generated a recombinant Listeria monocytogenes strain (rLM-E1) that secretes a model Ag encompassing the immunoproteasome-dependent E1B(192-200) and immunoproteasome-independent E1A(234-243) epitope.
188 17548590 Analyses of Ag presentation showed that infected gene-deficient professional APCs, lacking the immunosubunits LMP7/ibeta5 and MECL-1/ibeta2, processed and presented the rLM-E1-derived E1B(192-200) epitope but with delayed kinetics.
189 17548590 Accordingly, infected gene-deficient mice failed to respond to the otherwise immunodominant E1B(192-200) epitope but mounted normal CD8 T cell responses to E1A(234-243) which was processed by the same professional APCs, from the same rLM-E1 Ag.
190 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
191 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
192 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
193 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
194 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
195 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
196 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
197 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
198 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
199 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
200 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
201 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
202 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
203 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
204 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
205 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
206 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
207 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
208 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
209 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
210 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
211 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
212 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
213 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
214 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
215 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
216 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
217 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
218 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
219 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
220 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
221 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
222 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
223 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
224 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
225 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
226 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
227 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
228 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
229 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
230 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
231 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
232 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
233 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
234 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
235 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
236 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
237 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
238 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
239 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
240 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
241 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
242 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
243 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
244 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
245 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
246 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
247 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
248 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
249 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
250 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
251 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
252 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
253 17804688 CD14+ antigen-presenting cells in human dermis are less mature than their CD1a+ counterparts.
254 17804688 We recently demonstrated that three antigen-presenting cell (APC) subsets exist in the healthy human dermis, CD14(+) and CD1a(+) dermal APCs and migratory dermal Langerhans cells.
255 17804688 Here, we extend these findings by defining CD208 as an exclusive marker of migratory dermal Langerhans cells, confirming that migratory dermal Langerhans cells (CD1a(high) CD207(+) CD208(+)) and CD1a(+) dermal APCs (CD1a(mid) CD207(-) CD208(-)) are two distinct APC populations.
256 17804688 Using flow cytometry and multicolor fluorescence immunohistochemistry, we demonstrated that there were striking differences between CD1a(+) and CD14(+) dermal APCs in their expression of pattern recognition receptors and maturation markers.
257 17804688 Expression of Toll-like receptor (TLR) 2, CD206 and CD209 was largely restricted to CD14(+) dermal APCs.
258 17804688 Consistent with these observations, most CD14(+) dermal APCs expressed an immature phenotype when compared with CD1a(+) dermal APCs, which expressed high levels of the maturation marker CD83 on their cell surface.
259 17804688 However, a subset of CD14(+) dermal APCs also expressed cell-surface CD83, associated with a loss of cell-surface TLR2, suggesting that they have the capacity to mature.
260 17804688 CD14(+) dermal APCs are therefore the dominant cutaneous APC population capable of sensing ligands recognized by CD206, CD209 and TLR2 and subsequently may have the potential to mature.
261 17804688 CD68 expression was largely restricted to a subset of CD14(+) dermal APCs, while both CD14(+) and CD1a(+) dermal APCs expressed CD11b and CD11c.
262 17892515 In the present study, we investigated the efficacy of the HSP105-pulsed BM-DC vaccine on tumor regression in the Apc(Min/+) mouse.
263 17892515 Western blot and immunohistochemical analyses revealed that the tumors of the Apc(Min/+) mice endogenously overexpressed HSP105.
264 17892515 Immunization of the Apc(Min/+) mice with a HSP105-pulsed BM-DC vaccine at 6, 8, and 10 weeks of age significantly reduced the number of small-intestinal polyps accompanied by infiltration of both CD4(+) and CD8(+) T cells in the tumors.
265 17892515 Cell depletion experiments proved that both CD4(+) and CD8(+) T cells play a critical role in the activation of antitumor immunity induced by these vaccinations.
266 17892515 These findings indicate that the HSP105-pulsed BM-DC vaccine can provide potent immunotherapy for tumors that appear spontaneously as a result of the inactivation of a tumor suppressor gene, such as in the Apc(Min/+) mouse model.
267 17892515 In the present study, we investigated the efficacy of the HSP105-pulsed BM-DC vaccine on tumor regression in the Apc(Min/+) mouse.
268 17892515 Western blot and immunohistochemical analyses revealed that the tumors of the Apc(Min/+) mice endogenously overexpressed HSP105.
269 17892515 Immunization of the Apc(Min/+) mice with a HSP105-pulsed BM-DC vaccine at 6, 8, and 10 weeks of age significantly reduced the number of small-intestinal polyps accompanied by infiltration of both CD4(+) and CD8(+) T cells in the tumors.
270 17892515 Cell depletion experiments proved that both CD4(+) and CD8(+) T cells play a critical role in the activation of antitumor immunity induced by these vaccinations.
271 17892515 These findings indicate that the HSP105-pulsed BM-DC vaccine can provide potent immunotherapy for tumors that appear spontaneously as a result of the inactivation of a tumor suppressor gene, such as in the Apc(Min/+) mouse model.
272 17892515 In the present study, we investigated the efficacy of the HSP105-pulsed BM-DC vaccine on tumor regression in the Apc(Min/+) mouse.
273 17892515 Western blot and immunohistochemical analyses revealed that the tumors of the Apc(Min/+) mice endogenously overexpressed HSP105.
274 17892515 Immunization of the Apc(Min/+) mice with a HSP105-pulsed BM-DC vaccine at 6, 8, and 10 weeks of age significantly reduced the number of small-intestinal polyps accompanied by infiltration of both CD4(+) and CD8(+) T cells in the tumors.
275 17892515 Cell depletion experiments proved that both CD4(+) and CD8(+) T cells play a critical role in the activation of antitumor immunity induced by these vaccinations.
276 17892515 These findings indicate that the HSP105-pulsed BM-DC vaccine can provide potent immunotherapy for tumors that appear spontaneously as a result of the inactivation of a tumor suppressor gene, such as in the Apc(Min/+) mouse model.
277 17892515 In the present study, we investigated the efficacy of the HSP105-pulsed BM-DC vaccine on tumor regression in the Apc(Min/+) mouse.
278 17892515 Western blot and immunohistochemical analyses revealed that the tumors of the Apc(Min/+) mice endogenously overexpressed HSP105.
279 17892515 Immunization of the Apc(Min/+) mice with a HSP105-pulsed BM-DC vaccine at 6, 8, and 10 weeks of age significantly reduced the number of small-intestinal polyps accompanied by infiltration of both CD4(+) and CD8(+) T cells in the tumors.
280 17892515 Cell depletion experiments proved that both CD4(+) and CD8(+) T cells play a critical role in the activation of antitumor immunity induced by these vaccinations.
281 17892515 These findings indicate that the HSP105-pulsed BM-DC vaccine can provide potent immunotherapy for tumors that appear spontaneously as a result of the inactivation of a tumor suppressor gene, such as in the Apc(Min/+) mouse model.
282 17980936 The mechanism of stimulation of the immune system by this kind of vaccine is likely to be through the augmentation of APC maturation (a significantly increased proportion of CD86+ CD11c+ was determined in vaccinated mice), consequent activation of T lymphocytes (the proportions of CD25+ and CD69+ splenic lymphocytes increased after the exposure to activated DCs) and establishment of memory cells.
283 18056388 Improved protection against disseminated tuberculosis by Mycobacterium bovis bacillus Calmette-Guerin secreting murine GM-CSF is associated with expansion and activation of APCs.
284 18056388 BCG-derived GM-CSF stimulated the in vitro generation of functional APCs from murine bone marrow precursors, as demonstrated by the infection-induced secretion of IL-12 by differentiated APCs, and the ability of these cells to present Ag to mycobacterium-specific T cells.
285 18056388 The increased APC number was associated with an increase in the frequency of anti-mycobacterial IFN-gamma-secreting T cells generated after BCG:GM-CSF vaccination compared with vaccination with control BCG, and this effect was sustained up to 17 wk in the spleens of immunized mice.
286 18056388 Improved protection against disseminated tuberculosis by Mycobacterium bovis bacillus Calmette-Guerin secreting murine GM-CSF is associated with expansion and activation of APCs.
287 18056388 BCG-derived GM-CSF stimulated the in vitro generation of functional APCs from murine bone marrow precursors, as demonstrated by the infection-induced secretion of IL-12 by differentiated APCs, and the ability of these cells to present Ag to mycobacterium-specific T cells.
288 18056388 The increased APC number was associated with an increase in the frequency of anti-mycobacterial IFN-gamma-secreting T cells generated after BCG:GM-CSF vaccination compared with vaccination with control BCG, and this effect was sustained up to 17 wk in the spleens of immunized mice.
289 18381820 Earlier studies showed that depolymerization of polysaccharide A (PSA) from Bacteroides fragilis in the endosome depends on the APC's having an intact inducible nitric oxide synthase (iNOS) gene; the chemical mechanism underlying depolymerization of a carbohydrate within the endosome/lysosome is described here.
290 18381820 Examining the ability of the major RNSs to degrade PSA, we determined that deamination is the predominant mechanism for PSA processing in APCs and is a required step in PSA presentation to CD4(+) T cells by MHCII molecules.
291 18381820 Unlike native PSA, PSA-NO is presented by iNOS-deficient APCs to induce CD4(+) T cell proliferation.
292 18686103 Since T-regulatory cells and other T-cell subsets express TLR2, and TLR2 engagement modifies functionality and activation state of these cells, we speculate that most effects induced by natural and chemically derived ZPS may be explained by their TLR2 agonist properties, presumably through the combined action on TLR2-expressing APCs and T cells.
293 19017952 During T cell interaction with APC, CD28 is recruited to the central region (cSMAC) of the immunological synapse.
294 19017952 CD28-mediated signaling through PI3K results in the recruitment of protein kinase C-theta (PKCtheta) to the cSMAC, activation of NF-kappaB, and up-regulation of IL-2 transcription.
295 19017952 In this report, we show that CD28 recruitment and persistence at the immunological synapse requires TCR signals and CD80 engagement.
296 19017952 Addition of mAb to either MHC class II or CD80 results in the rapid displacement of CD28 from the immunological synapse.
297 19017952 Ligand binding is not sufficient for CD28 localization to the immunological synapse, as truncation of the cytosolic tail of CD28 disrupts synapse localization without effecting the ability of CD28 to bind CD80.
298 19017952 Mutation of tyrosine 188 also results in diminished activation of NF-kappaB, suggesting that CD28-mediated localization of PKCtheta to the cSMAC is important for efficient signal transduction.
299 19124733 The magnitude and quality of the CD8+ T cell response are regulated by the interplay between the size of the APC population and duration of Ag presentation.
300 19404546 Here, we present novel insights into the participation of DV in the downregulation of the thrombomodulin-thrombin-protein C complex formation at the endothelial surface, with a reduction in activated protein C (APC).
301 19404546 APC is the most important vasoprotective protein because it downregulates thrombin generation (by the inactivation of procoagulant factors Va and VIIIa) and has anti-inflammatory, antiapoptotic, and barrier protection properties.
302 19404546 These biological functions of APC are associated with the endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR-1) signalling pathways, which link the coagulation-inflammation responses.
303 19404546 Here, we present novel insights into the participation of DV in the downregulation of the thrombomodulin-thrombin-protein C complex formation at the endothelial surface, with a reduction in activated protein C (APC).
304 19404546 APC is the most important vasoprotective protein because it downregulates thrombin generation (by the inactivation of procoagulant factors Va and VIIIa) and has anti-inflammatory, antiapoptotic, and barrier protection properties.
305 19404546 These biological functions of APC are associated with the endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR-1) signalling pathways, which link the coagulation-inflammation responses.
306 19404546 Here, we present novel insights into the participation of DV in the downregulation of the thrombomodulin-thrombin-protein C complex formation at the endothelial surface, with a reduction in activated protein C (APC).
307 19404546 APC is the most important vasoprotective protein because it downregulates thrombin generation (by the inactivation of procoagulant factors Va and VIIIa) and has anti-inflammatory, antiapoptotic, and barrier protection properties.
308 19404546 These biological functions of APC are associated with the endothelial protein C receptor (EPCR) and protease-activated receptor 1 (PAR-1) signalling pathways, which link the coagulation-inflammation responses.
309 19494321 Bone marrow-derived mesenchymal stromal cells (MSC) possess an immune plasticity manifested by either an immunosuppressive or, when activated with IFN-gamma, an APC phenotype.
310 19494321 We observed that human MSC and macrophages expressed TLR3 and TLR4 at comparable levels and TLR-mediated activation of MSC resulted in the production of inflammatory mediators such as IL-1beta, IL-6, IL-8/CXCL8, and CCL5.
311 19494321 IFN-alpha or IFN-gamma priming up-regulated production of these inflammatory mediators and expression of IFNB, inducible NO synthase (iNOS), and TRAIL upon TLR activation in MSC and macrophages, but failed to induce IL-12 and TNF-alpha production in MSC.
312 19494321 In addition, IFN priming combined with TLR activation may increase immune responses induced by Ag-presenting MSC through presentation of Ag in an inflammatory context, a mechanism that could be applied in a cell-based vaccine.
313 19776199 In this study, we directly compared murine CD11c+ APCs isolated from colon, lung, and spleen and found that APCs isolated from these tissues differ considerably in Toll-like receptor (TLR) expression and responses to in vitro TLR ligand stimulation.
314 19776199 We also provide evidence that tissue microenvironments dictate distinct patterns of TLR expression by CD11c+ APCs in different mucosal tissues.
315 19776199 In this study, we directly compared murine CD11c+ APCs isolated from colon, lung, and spleen and found that APCs isolated from these tissues differ considerably in Toll-like receptor (TLR) expression and responses to in vitro TLR ligand stimulation.
316 19776199 We also provide evidence that tissue microenvironments dictate distinct patterns of TLR expression by CD11c+ APCs in different mucosal tissues.
317 19882154 A culture of isolated tumor-infiltrated CD11b cells in the presence of AZA and GM-CSF promoted their differentiation into mature F4/80/CD11c/MHC class II-positive APCs.
318 19882154 These tumor-derived myeloid APCs produced substantially reduced amounts of immunosuppressive (IL-13, IL-10, PGE(2)), pro-angiogenic (VEGF, MMP-9) and pro-inflammatory (IL-1beta, IL-6, MIP-2) mediators than their precursors, freshly isolated tumor-infiltrated CD11b cells.
319 19882154 A culture of isolated tumor-infiltrated CD11b cells in the presence of AZA and GM-CSF promoted their differentiation into mature F4/80/CD11c/MHC class II-positive APCs.
320 19882154 These tumor-derived myeloid APCs produced substantially reduced amounts of immunosuppressive (IL-13, IL-10, PGE(2)), pro-angiogenic (VEGF, MMP-9) and pro-inflammatory (IL-1beta, IL-6, MIP-2) mediators than their precursors, freshly isolated tumor-infiltrated CD11b cells.
321 19962962 Here we described a method for delivering whole protein antigens to APCs via carbohydrate-mediated targeting of Dectin-1, which is a C-type lectin and mainly expresses on subpopulations of dendritic cells and macrophages.
322 19962962 Taken together, our data suggest that APCs targeting based on glucan-Dectin-1 interaction is a promising approach to improve vaccines.
323 19962962 Here we described a method for delivering whole protein antigens to APCs via carbohydrate-mediated targeting of Dectin-1, which is a C-type lectin and mainly expresses on subpopulations of dendritic cells and macrophages.
324 19962962 Taken together, our data suggest that APCs targeting based on glucan-Dectin-1 interaction is a promising approach to improve vaccines.
325 21149605 Antibody-targeted NY-ESO-1 to mannose receptor or DEC-205 in vitro elicits dual human CD8+ and CD4+ T cell responses with broad antigen specificity.
326 21149605 Immunization of cancer patients with vaccines containing full-length tumor Ags aims to elicit specific Abs and both CD4(+) and CD8(+) T cells.
327 21149605 Vaccination with protein Ags, however, often elicits only CD4(+) T cell responses without inducing Ag-specific CD8(+) T cells, as exogenous protein is primarily presented to CD4(+) T cells.
328 21149605 Recent data revealed that Ab-mediated targeting of protein Ags to cell surface receptors on dendritic cells could enhance the induction of both CD4(+) and CD8(+) T cells.
329 21149605 We generated two novel targeting proteins consisting of the full-length NY-ESO-1 fused to the C terminus of two human mAbs against the human mannose receptor and DEC-205, both internalizing molecules expressed on APC.
330 21149605 These targeting proteins were evaluated for their ability to activate NY-ESO-1-specific human CD4(+) and CD8(+) T cells in vitro.
331 21149605 Whereas nontargeted and Ab-targeted NY-ESO-1 proteins similarly activated CD4(+) T cells, cross-presentation to CD8(+) T cells was only efficiently induced by targeted NY-ESO-1.
332 21149605 In addition, both mannose receptor and DEC-205 targeting elicited specific CD4(+) and CD8(+) T cells from PBLs of cancer patients.
333 21149605 Receptor-specific delivery of NY-ESO-1 to APC appears to be a promising vaccination strategy to efficiently generate integrated and broad Ag-specific immune responses against NY-ESO-1 in cancer patients.
334 21483862 In fact, injection of α-GalCer-loaded CD1d-/- BM-DCs resulted in potent iNKT cell activation, suggesting that this glycolipid antigen can also be transferred to resident CD1d+ APCs.
335 22006508 Complexes with biotinylated antibodies targeting cell surface receptors are formed and used to deliver the Ags of choice for processing and presentation by APCs and induction of Ag-specific CD4+ and CD8+ T-cell responses in vitro and in vivo.
336 22573738 We demonstrated that direct exposure of porcine APCs to L. jensenii in the absence of inflammatory signals increased expression of interleukin-10 (IL-10) and transforming growth factor β in CD172a(+) APCs and caused them to display tolerogenic properties.
337 22573738 In addition, pretreatment of CD172a(+) APCs with L. jensenii resulted in differential modulation of the production of pro- and anti-inflammatory cytokines in response to TLR4 activation.
338 22573738 The immunomodulatory effect of strain TL2937 was not related to a downregulation of TLR4 but was related to an upregulation of the expression of three negative regulators of TLRs: single immunoglobulin IL-1-related receptor (SIGIRR), A20, and interleukin-1 receptor-associated kinase M (IRAK-M).
339 22573738 Our results also indicated that TLR2 has an important role in the anti-inflammatory activity of L. jensenii TL2937, since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M in CD172a(+) APCs and the production of IL-10 in response to TLR4 activation.
340 22573738 We demonstrated that direct exposure of porcine APCs to L. jensenii in the absence of inflammatory signals increased expression of interleukin-10 (IL-10) and transforming growth factor β in CD172a(+) APCs and caused them to display tolerogenic properties.
341 22573738 In addition, pretreatment of CD172a(+) APCs with L. jensenii resulted in differential modulation of the production of pro- and anti-inflammatory cytokines in response to TLR4 activation.
342 22573738 The immunomodulatory effect of strain TL2937 was not related to a downregulation of TLR4 but was related to an upregulation of the expression of three negative regulators of TLRs: single immunoglobulin IL-1-related receptor (SIGIRR), A20, and interleukin-1 receptor-associated kinase M (IRAK-M).
343 22573738 Our results also indicated that TLR2 has an important role in the anti-inflammatory activity of L. jensenii TL2937, since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M in CD172a(+) APCs and the production of IL-10 in response to TLR4 activation.
344 22595444 Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance.
345 22875619 We isolated phenotypically defined CD4(+) T-cell subpopulations from circulating lymphocytes of DR52b(+) healthy donors by flow cytometry cell sorting and stimulated them in vitro with peptide ESO(119-143), autologous APC and IL-2.
346 22875619 We isolated ESO-tetramer(+) cells by flow cytometry cell sorting and expanded them with PHA, APC and IL-2 to generate ESO-specific T(H) lines.
347 22875619 Using this approach, we could consistently generate ESO-tetramer(+) T(H) lines from conventional CD4(+)CD25(-) naïve and central memory populations, but not from effector memory populations or CD4(+)CD25(+) Treg.
348 22875619 We isolated phenotypically defined CD4(+) T-cell subpopulations from circulating lymphocytes of DR52b(+) healthy donors by flow cytometry cell sorting and stimulated them in vitro with peptide ESO(119-143), autologous APC and IL-2.
349 22875619 We isolated ESO-tetramer(+) cells by flow cytometry cell sorting and expanded them with PHA, APC and IL-2 to generate ESO-specific T(H) lines.
350 22875619 Using this approach, we could consistently generate ESO-tetramer(+) T(H) lines from conventional CD4(+)CD25(-) naïve and central memory populations, but not from effector memory populations or CD4(+)CD25(+) Treg.
351 24041689 Co-stimulatory signaling pathway triggered by the binding of B7.1/B7.2 (CD80/86) of antigen-presenting cells (APCs) to CD28 of T cells is required for optimal T-cell activation.
352 24041689 Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding with a greater affinity.
353 24041689 To develop a novel therapeutics specifically targeting CTLA-4, we constructed a DNA vaccine by cloning the sequence of CTLA-4 fused with a transmembrane domain sequence of placental alkaline phosphatase (PLAP) into a mammalian expression plasmid, pVAC-1.
354 24778318 We explored the interaction of the tumor-derived heat shock proteins (HSP) with their common receptor (CD91) on antigen-presenting cells (APC) as a mechanism for host-priming of T-cell-mediated antitumor immunity.
355 24778318 Using targeted genetic disruption of the interaction between HSPs and CD91, we demonstrated that specific ablation of CD91 in APCs prevented the establishment of antitumor immunity.
356 24778318 The antitumor immunity was also inhibited when the transfer of tumor-derived HSPs to APCs was prevented using an endogenous inhibitor of CD91.
357 24778318 We explored the interaction of the tumor-derived heat shock proteins (HSP) with their common receptor (CD91) on antigen-presenting cells (APC) as a mechanism for host-priming of T-cell-mediated antitumor immunity.
358 24778318 Using targeted genetic disruption of the interaction between HSPs and CD91, we demonstrated that specific ablation of CD91 in APCs prevented the establishment of antitumor immunity.
359 24778318 The antitumor immunity was also inhibited when the transfer of tumor-derived HSPs to APCs was prevented using an endogenous inhibitor of CD91.
360 25175154 In this study, a solid-liquid interfacial shear device was used to investigate the shear response of aluminum phosphate adjuvant alone and two adjuvant containing vaccine drug products (DP1 and DP2).
361 26148331 We observed that at d 3-4 post vaccination, 6 genes were down-regulated, namely APC, CD3G, FASLG, IL7, CD8A and TLR1.
362 26148331 Meanwhile at 6-7 days post vaccination, 9 genes were significantly up-regulated, including RIPK2, TGFB1, MICB, SOCS1, IL2RA, MS4A1, PTPRC, IL2 and IL8.
363 26148331 By days 12-15 the genes RIPK2, IL4, IL12B and TLR2 were overexpressed.
364 26231333 Expression of surface markers on APCs (CD80, CD86) and T-cells (CD4+, CD8+) was also evaluated.