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Gene Information

Gene symbol: LAMP1

Gene name: lysosomal-associated membrane protein 1

HGNC ID: 6499

Synonyms: CD107a

Related Genes

# Gene Symbol Number of hits
1 APLP2 1 hits
2 BAK1 1 hits
3 BAX 1 hits
4 BCL2L1 1 hits
5 C20orf181 1 hits
6 C8orf4 1 hits
7 CALR 1 hits
8 CASP3 1 hits
9 CCL4 1 hits
10 CCR7 1 hits
11 CD27 1 hits
12 CD4 1 hits
13 CD44 1 hits
14 CD63 1 hits
15 CD69 1 hits
16 CD8A 1 hits
17 CTSD 1 hits
18 EEA1 1 hits
19 ERBB2 1 hits
20 ERVWE1 1 hits
21 GZMA 1 hits
22 GZMB 1 hits
23 HLA-A 1 hits
24 HLA-DOA 1 hits
25 HSPA1A 1 hits
26 IFNG 1 hits
27 IL10 1 hits
28 IL13 1 hits
29 IL17A 1 hits
30 IL2 1 hits
31 IL4 1 hits
32 ISG20 1 hits
33 ITGAE 1 hits
34 ITGAX 1 hits
35 IV 1 hits
36 KIR3DL1 1 hits
37 KLRD1 1 hits
38 KLRG1 1 hits
39 LAMP2 1 hits
40 LAMP3 1 hits
41 LTA 1 hits
42 MAPT 1 hits
43 MLANA 1 hits
44 PLAT 1 hits
45 RAB4A 1 hits
46 RAB5A 1 hits
47 RPS27A 1 hits
48 SELL 1 hits
49 TBX21 1 hits
50 TERT 1 hits
51 TFRC 1 hits
52 TLR3 1 hits
53 TNF 1 hits
54 TNFRSF9 1 hits
55 TPD52 1 hits
56 WT1 1 hits
57 ZMYND10 1 hits

Related Sentences

# PMID Sentence
1 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.
2 7636236 The enhanced stimulatory capacity of APC expressing LAMP-1-targeted Ags has important implications for vaccine design.
3 8524826 The presentation of antigenic peptides by major histocompatibility complex (MHC) class II molecules to CD4+ T cells is critical to the function of the immune system.
4 8524826 The LAMP-1 sorting signal reroutes the antigen into the MHC class II processing pathway, resulting in enhanced presentation to CD4+ cells in vitro.
5 8548765 Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
6 8548765 In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
7 8548765 Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
8 8548765 All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
9 8548765 Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
10 8548765 Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
11 8548765 In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
12 8548765 Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
13 8548765 All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
14 8548765 Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
15 8548765 Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
16 8548765 In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
17 8548765 Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
18 8548765 All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
19 8548765 Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
20 10584920 In addition, mice vaccinated with Sig/E7/LAMP-1 DNA had greater numbers of E7-specific CD4+ helper T cells, higher E7-specific CTL activity, and greater numbers of CD8+ T cell precursors than did mice vaccinated with Sig/E7 or wild-type E7 DNA.
21 10637448 Mice vaccinated with Sig/E7/LAMP-1 DNA generated the strongest E7-specific CTL activities, the highest numbers of E7-specific CD8+ cell precursors and the highest titers of E7-specific antibodies.
22 10706963 We found that priming with Sig/E7/LAMP-1 DNA and boosting with Vac-Sig/E7/LAMP-1 generated the strongest E7-specific CD8(+) T cell responses.
23 10940924 One peptide was presented better from the TFR fusion protein, while all others were presented better from the LAMP-1 construct.
24 11160307 Confocal microscopy studies revealed that wH22xeGFP was rapidly internalized by the high-FcgammaRI-expressing cell line U937 10.6, but did not associate with intracellular proteins Rab4, Rab5a, or Lamp-1, suggesting that the targeted fusion protein was not localized in early endosomes, recycling vesicles, or lysosomes.
25 11177561 Furthermore, our data revealed that CD8(+) T cells, CD4(+) T cells, and NK cells were important for the antitumor effects generated by Sig/E7/LAMP-1 RNA vaccination.
26 11313782 We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
27 11313782 At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
28 11313782 Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
29 11313782 Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
30 11313782 We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
31 11313782 We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
32 11313782 At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
33 11313782 Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
34 11313782 Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
35 11313782 We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
36 11313782 We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
37 11313782 At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
38 11313782 Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
39 11313782 Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
40 11313782 We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
41 11313782 We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
42 11313782 At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
43 11313782 Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
44 11313782 Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
45 11313782 We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
46 11313782 We previously found that recombinant vaccinia and naked DNA vaccines containing the chimeric Sig/E7/LAMP-1 gene were capable of controlling the growth of HPV-16 E7-expressing tumor cells (TC-1).
47 11313782 At a dose of 1 x 10(6) TC-1 cells per mouse, Sig/E7/LAMP-1 DNA provided 100% protection against subcutaneous growth of tumors, while Vac-Sig/E7/LAMP-1 protected only 40% of the mice.
48 11313782 Furthermore, Sig/E7/LAMP-1 DNA vaccines are capable of protecting against challenge with a more stringent subclone of TC-1 (TC-1 P2) established from TC-1 tumors that survived initial Sig/E7/LAMP-1 vaccinia vaccination.
49 11313782 Interestingly, Sig/E7/LAMP-1 vaccinia induced both E7-specific IFN-gamma- and IL4-secreting CD4(+) T cell precursors while Sig/E7/LAMP-1 DNA induced only E7-specific IFN-gamma-secreting CD4(+) T cell precursors.
50 11313782 We also found that IL-4 knockout C57BL/6 mice vaccinated with Sig/E7/LAMP-1 vaccinia exhibited a more potent antitumor effect than vaccinated wild-type C57BL/6 mice in our tumor protection experiments.
51 12208759 In this study, we sought to determine whether human DCs transfected with mRNA encoding a chimeric hTERT/lysosome-associated membrane protein (LAMP-1) protein, carrying the endosomal/lysosomal sorting signal of the LAMP-1, are capable of stimulating concomitant hTERT-specific CD8(+) and CD4(+) T-cell responses in vitro.
52 12208759 We show that processing of hTERT/LAMP-1 transcripts leads to enhanced stimulation of hTERT-specific CD4(+) T cells and does not negatively affect intracellular generation and subsequent presentation of MHC class I epitopes, hence, generating a CTL response.
53 12208759 These findings provide a preclinical rationale of using DCs transfected with the chimeric hTERT/LAMP-1 RNA in vaccine trials to facilitate generation of antigen-specific CD4(+) T-cell responses that may be required to stimulate and maintain an optimal CD8(+) CTL response in vivo.
54 12208759 In this study, we sought to determine whether human DCs transfected with mRNA encoding a chimeric hTERT/lysosome-associated membrane protein (LAMP-1) protein, carrying the endosomal/lysosomal sorting signal of the LAMP-1, are capable of stimulating concomitant hTERT-specific CD8(+) and CD4(+) T-cell responses in vitro.
55 12208759 We show that processing of hTERT/LAMP-1 transcripts leads to enhanced stimulation of hTERT-specific CD4(+) T cells and does not negatively affect intracellular generation and subsequent presentation of MHC class I epitopes, hence, generating a CTL response.
56 12208759 These findings provide a preclinical rationale of using DCs transfected with the chimeric hTERT/LAMP-1 RNA in vaccine trials to facilitate generation of antigen-specific CD4(+) T-cell responses that may be required to stimulate and maintain an optimal CD8(+) CTL response in vivo.
57 12208759 In this study, we sought to determine whether human DCs transfected with mRNA encoding a chimeric hTERT/lysosome-associated membrane protein (LAMP-1) protein, carrying the endosomal/lysosomal sorting signal of the LAMP-1, are capable of stimulating concomitant hTERT-specific CD8(+) and CD4(+) T-cell responses in vitro.
58 12208759 We show that processing of hTERT/LAMP-1 transcripts leads to enhanced stimulation of hTERT-specific CD4(+) T cells and does not negatively affect intracellular generation and subsequent presentation of MHC class I epitopes, hence, generating a CTL response.
59 12208759 These findings provide a preclinical rationale of using DCs transfected with the chimeric hTERT/LAMP-1 RNA in vaccine trials to facilitate generation of antigen-specific CD4(+) T-cell responses that may be required to stimulate and maintain an optimal CD8(+) CTL response in vivo.
60 12960321 We have also demonstrated that DNA vaccines targeting Ag to subcellular compartments, using proteins such as Mycobacterium tuberculosis heat shock protein 70, calreticulin, or the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1), enhanced DNA vaccine potency.
61 12960321 We showed that coadministration of DNA encoding Bcl-x(L) with DNA encoding E7/heat shock protein 70, calreticulin/E7, or Sig/E7/LAMP-1 resulted in further enhancement of the E7-specific CD8(+) T cell response for all three constructs.
62 12960321 Of these strategies, mice vaccinated with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA showed the greatest increase in E7-specific CD8(+) T cells ( approximately 13-fold increase).
63 12960321 This combination of strategies resulted in increased CD8(+) T cell functional avidity, an increased E7-specific CD4(+) Th1 cell response, enhanced tumor treatment ability, and stronger long-term tumor protection when compared with mice vaccinated without Bcl-x(L) DNA.
64 12960321 We have also demonstrated that DNA vaccines targeting Ag to subcellular compartments, using proteins such as Mycobacterium tuberculosis heat shock protein 70, calreticulin, or the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1), enhanced DNA vaccine potency.
65 12960321 We showed that coadministration of DNA encoding Bcl-x(L) with DNA encoding E7/heat shock protein 70, calreticulin/E7, or Sig/E7/LAMP-1 resulted in further enhancement of the E7-specific CD8(+) T cell response for all three constructs.
66 12960321 Of these strategies, mice vaccinated with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA showed the greatest increase in E7-specific CD8(+) T cells ( approximately 13-fold increase).
67 12960321 This combination of strategies resulted in increased CD8(+) T cell functional avidity, an increased E7-specific CD4(+) Th1 cell response, enhanced tumor treatment ability, and stronger long-term tumor protection when compared with mice vaccinated without Bcl-x(L) DNA.
68 12960321 We have also demonstrated that DNA vaccines targeting Ag to subcellular compartments, using proteins such as Mycobacterium tuberculosis heat shock protein 70, calreticulin, or the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1), enhanced DNA vaccine potency.
69 12960321 We showed that coadministration of DNA encoding Bcl-x(L) with DNA encoding E7/heat shock protein 70, calreticulin/E7, or Sig/E7/LAMP-1 resulted in further enhancement of the E7-specific CD8(+) T cell response for all three constructs.
70 12960321 Of these strategies, mice vaccinated with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA showed the greatest increase in E7-specific CD8(+) T cells ( approximately 13-fold increase).
71 12960321 This combination of strategies resulted in increased CD8(+) T cell functional avidity, an increased E7-specific CD4(+) Th1 cell response, enhanced tumor treatment ability, and stronger long-term tumor protection when compared with mice vaccinated without Bcl-x(L) DNA.
72 14580882 CD107a and b are expressed on the cell surface of CD8+ T cells following activation with cognate peptide, concordant with production of intracellular IFNgamma.
73 14580882 Measurement of CD107a and b expression can also be combined with MHC-class I tetramer labeling and intracellular cytokine staining to provide a more complete assessment of the functionality of CD8+T cells expressing cognate T cell receptors (TCR).
74 14580882 CD107a and b are expressed on the cell surface of CD8+ T cells following activation with cognate peptide, concordant with production of intracellular IFNgamma.
75 14580882 Measurement of CD107a and b expression can also be combined with MHC-class I tetramer labeling and intracellular cytokine staining to provide a more complete assessment of the functionality of CD8+T cells expressing cognate T cell receptors (TCR).
76 14985791 These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat-shock protein 70 (HSP70), calreticulin (CRT) and the translocation domain (dII) of Pseudomonas aeruginosa exotoxin A (ETA).
77 14985791 Vaccination with DNA vaccines encoding E7 antigen linked to any of these molecules all led to a significant enhancement of E7-specific CD8(+) T-cell immune responses and strong antitumor effects against an E7-expressing tumor, TC-1.
78 15153480 Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules.
79 15153480 An optimal anticancer vaccine probably requires the cooperation of both CD4(+) Th cells and CD8(+) CTLs.
80 15153480 In this study we compared the efficiency of the targeting signals of invariant chain, lysosome-associated membrane protein-1 (LAMP1) and DC-LAMP.
81 15153480 DCs were also electroporated with unmodified MAGE-A3 or MAGE-A3 linked to the targeting signals, and the presentation of MAGE-A3-derived epitopes in the context of HLA class I and class II molecules was investigated.
82 15153480 Proteins linked to the LAMP1 or DC-LAMP signal are more efficiently presented than proteins linked to the invariant chain-targeting signal.
83 15153480 Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules.
84 15153480 An optimal anticancer vaccine probably requires the cooperation of both CD4(+) Th cells and CD8(+) CTLs.
85 15153480 In this study we compared the efficiency of the targeting signals of invariant chain, lysosome-associated membrane protein-1 (LAMP1) and DC-LAMP.
86 15153480 DCs were also electroporated with unmodified MAGE-A3 or MAGE-A3 linked to the targeting signals, and the presentation of MAGE-A3-derived epitopes in the context of HLA class I and class II molecules was investigated.
87 15153480 Proteins linked to the LAMP1 or DC-LAMP signal are more efficiently presented than proteins linked to the invariant chain-targeting signal.
88 15153784 We have shown that DNA encoding the anti-apoptotic protein Bcl-xL enhances E7-specific CD8+ T-cell responses and DNA encoding pro-apoptotic protein caspase-3 suppresses E7-specific CD8+ T-cell responses when co-administered intradermally via gene gun with DNA encoding human papillomavirus type 16 (HPV-16) E7 linked to the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1).
89 15153784 We vaccinated C57BL/6 mice with pVITRO-SEL-Bcl-xL, pVITRO-SEL-mtBcl-xL, pVITRO-SEL, or pVITRO-SEL-caspase-3 intradermally via gene gun and intramuscularly via injection.
90 15153784 We demonstrated that vaccination with pVITRO achieved similar results to a co-administration strategy: that Bcl-xL enhanced the E7-specific CTL response and caspase-3 suppressed the E7-specific CTL response.
91 15153784 Thus, intradermal vaccination with a pVITRO vector combining an anti-apoptotic strategy (Bcl-xL) and an intracellular targeting strategy (SEL) further enhances the E7-specific CD8+ T-cell response and guarantees co-expression of both encoded molecules in transfected cells.
92 15155622 We assessed the maturation of the F. tularensis phagosome by examining its acquisition of the lysosome-associated membrane glycoproteins (LAMPs) CD63 and LAMP1 and the acid hydrolase cathepsin D.
93 15155622 Two to four hours after infection, vacuoles containing live F. tularensis cells acquired abundant staining for LAMPs but little or no staining for cathepsin D.
94 15155622 These results indicate that F. tularensis initially enters a nonacidified phagosome with LAMPs but without cathepsin D and that the phagosomal membrane subsequently becomes morphologically disrupted, allowing the bacteria to gain direct access to the macrophagic cytoplasm.
95 15193918 Inverted terminal repeat sequences of adeno-associated virus enhance the antibody and CD8(+) responses to a HIV-1 p55Gag/LAMP DNA vaccine chimera.
96 15193918 The immune responses to an HIV-1 p55Gag vaccine encoded as a DNA chimera with the lysosomal associated membrane protein-1 (LAMP) have been examined for the effect of the addition of the inverted terminal repeat (ITR) sequences of the adeno-associated virus (AAV) to the DNA plasmid construct, and of packaging the LAMP/gag gene as a recombinant AAV vector (rAAV).
97 15193918 The results demonstrated that under DNA prime/DNA boost protocol, the "naked" DNA vaccines encoding the LAMP/gag chimera, either as pcDNA3.1 or pITR DNA plasmid constructs, elicited strong CD4(+) T cell responses.
98 15650058 Molecular modification of idiotypes from B-cell lymphomas for expression in mature dendritic cells as a strategy to induce tumor-reactive CD4+ and CD8+ T-cell responses.
99 15650058 This study exploited a molecular approach to modify the Id of 38C13 lymphoma for processing via class I and II antigen-processing pathways and evaluated protein expression in dendritic cells (DCs) to simultaneously stimulate tumor reactive CD8(+) and CD4(+) lymphocytes.
100 15650058 Recombinant vaccinia viruses (rVVs) were constructed, coding for Id fused with the targeting signal of the lysosomal-associated membrane protein1 (Id-LAMP1) to promote antigen presentation in the context of major histocompatibility complex (MHC) class II.
101 15650058 Mature DCs infected with rVV/Id-LAMP1 elicited both CD4(+) and CD8(+) Id-specific T cells and protected animals from tumor challenge.
102 15650058 Id-specific CD8(+) cells were required to mediate the effector phase of a therapeutic response, and CD4(+) cells were beneficial in the induction phase of the response.
103 15650058 These results demonstrate that fusing Id to LAMP1 enhances CD8(+) and CD4(+) Id-specific responses for NHLs and may be useful therapeutically.
104 15650058 Molecular modification of idiotypes from B-cell lymphomas for expression in mature dendritic cells as a strategy to induce tumor-reactive CD4+ and CD8+ T-cell responses.
105 15650058 This study exploited a molecular approach to modify the Id of 38C13 lymphoma for processing via class I and II antigen-processing pathways and evaluated protein expression in dendritic cells (DCs) to simultaneously stimulate tumor reactive CD8(+) and CD4(+) lymphocytes.
106 15650058 Recombinant vaccinia viruses (rVVs) were constructed, coding for Id fused with the targeting signal of the lysosomal-associated membrane protein1 (Id-LAMP1) to promote antigen presentation in the context of major histocompatibility complex (MHC) class II.
107 15650058 Mature DCs infected with rVV/Id-LAMP1 elicited both CD4(+) and CD8(+) Id-specific T cells and protected animals from tumor challenge.
108 15650058 Id-specific CD8(+) cells were required to mediate the effector phase of a therapeutic response, and CD4(+) cells were beneficial in the induction phase of the response.
109 15650058 These results demonstrate that fusing Id to LAMP1 enhances CD8(+) and CD4(+) Id-specific responses for NHLs and may be useful therapeutically.
110 15703486 We have previously shown that intradermal coadministration of DNA encoding Bcl-x(L), an antiapoptotic protein, with DNA encoding E7 antigen linked to the sorting signal of the lysosome-associated membrane protein type 1 (Sig/E7/LAMP-1) prolongs dendritic cell life and enhances antigen presentation through the MHC class I and II pathways.
111 15703486 Mice primed and boosted with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA generated significantly higher numbers of E7-specific CD8(+) memory T cells and a better long-term protective antitumor effect compared with mice primed with Sig/E7/LAMP-1 DNA and boosted with Sig/E7/LAMP-1 vaccinia (Vac-Sig/E7/LAMP-1).
112 15703486 Furthermore, coadministration of Sig/E7 /LAMP-1 DNA mixed with Bcl-x(L) DNA also generated higher avidity E7-specific CD8(+) T cells than did vaccination with Sig/E7/LAMP-1 DNA followed by a Vac-Sig/E7/LAMP-1 booster.
113 15703486 We have previously shown that intradermal coadministration of DNA encoding Bcl-x(L), an antiapoptotic protein, with DNA encoding E7 antigen linked to the sorting signal of the lysosome-associated membrane protein type 1 (Sig/E7/LAMP-1) prolongs dendritic cell life and enhances antigen presentation through the MHC class I and II pathways.
114 15703486 Mice primed and boosted with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA generated significantly higher numbers of E7-specific CD8(+) memory T cells and a better long-term protective antitumor effect compared with mice primed with Sig/E7/LAMP-1 DNA and boosted with Sig/E7/LAMP-1 vaccinia (Vac-Sig/E7/LAMP-1).
115 15703486 Furthermore, coadministration of Sig/E7 /LAMP-1 DNA mixed with Bcl-x(L) DNA also generated higher avidity E7-specific CD8(+) T cells than did vaccination with Sig/E7/LAMP-1 DNA followed by a Vac-Sig/E7/LAMP-1 booster.
116 15703486 We have previously shown that intradermal coadministration of DNA encoding Bcl-x(L), an antiapoptotic protein, with DNA encoding E7 antigen linked to the sorting signal of the lysosome-associated membrane protein type 1 (Sig/E7/LAMP-1) prolongs dendritic cell life and enhances antigen presentation through the MHC class I and II pathways.
117 15703486 Mice primed and boosted with Sig/E7/LAMP-1 DNA mixed with Bcl-x(L) DNA generated significantly higher numbers of E7-specific CD8(+) memory T cells and a better long-term protective antitumor effect compared with mice primed with Sig/E7/LAMP-1 DNA and boosted with Sig/E7/LAMP-1 vaccinia (Vac-Sig/E7/LAMP-1).
118 15703486 Furthermore, coadministration of Sig/E7 /LAMP-1 DNA mixed with Bcl-x(L) DNA also generated higher avidity E7-specific CD8(+) T cells than did vaccination with Sig/E7/LAMP-1 DNA followed by a Vac-Sig/E7/LAMP-1 booster.
119 15717275 Their cytotoxic functionality was evaluated by use of an assay that measures transient surface levels of lysosomal membrane proteins LAMP-1 (CD107a) and LAMP-2 (CD107b) after peptide stimulation.
120 15980996 Evaluation of the CD107 cytotoxicity assay for the detection of cytolytic CD8+ cells recognizing HER2/neu vaccine peptides.
121 15980996 Specifically, we investigated the use of the novel CD107 cytotoxicity assay in the detection of influenza and HER2/neu tumor-specific cytolytic CD8+ T cells.
122 15980996 CD8+ T cells from HLA-A2+ healthy donors were stimulated with autologous dendritic cells pulsed with FluM or the HER2/neu peptides, E75 or GP2.
123 15980996 Cytotoxicity was measured by detection of CD107a and b on the surface of CD8+ T cells.
124 15980996 E75- and GP2-stimulated CD8+ T cells were then tested in cytotoxicity assays with MCF-7 (HER2/neu+HLA-A2+) and AU565 (HER2/neu+HLA-A2-) tumor cells.
125 16170753 Flow-cytometric detection of vaccinia-induced memory effector CD4(+), CD8(+), and gamma delta TCR(+) T cells capable of antigen-specific expansion and effector functions.
126 16170753 Absolute numbers of CD4(+)/CFSE(lo)/interferon (IFN)- gamma (+), CD8(+)/CFSE(lo)/IFN- gamma (+), CD8(+)/CFSE(lo)/granzyme A(+), and CD8(+)/CFSE(lo)/CD107a(+) T cells present after in vitro stimulation with live vaccinia were significantly higher in immunized individuals (P<.05).
127 16170753 These CD4(+) and CD8(+) T cell increases were >2 log higher than increases detectable by standard lymphoproliferation and cytotoxicity assays.
128 16170753 Vaccinia-specific CD8(+)/CFSE(lo)/IFN- gamma (+) and granzyme A(+) T cell responses were significantly correlated with the results of standard (51)Cr-release cytolytic assays (P<.05).
129 16170753 We demonstrate that vaccinia induces robust memory effector CD4(+), CD8(+), and gamma delta T cells, all of which are relevant for protection against smallpox.
130 16200349 These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat shock protein 70 (HSP70), calreticulin (CRT) and herpes simplex virus type 1 (HSV-1) VP22 proteins.
131 16200349 In the current study, we have characterized DNA vaccines employing these intracellular targeting or intercellular spreading strategies targeting HPV-16 E6 for their ability to generate E6-specific CD8+ T cell immune responses and antitumor effects against an E6-expressing tumor cell line, TC-1, in C57BL/6 mice.
132 16200349 We found that all the intracellular targeting strategies (CRT, LAMP-1, HSP70) as well as the intercellular spreading strategy (VP22) were able to enhance E6 DNA vaccine potency, although the orientation of HSP70 linked to E6 antigen in the E6 DNA vaccine appears to be important for the HSP70 strategy to work.
133 16200349 The enhanced E6-specific CD8+ T cell immune response in vaccinated mice also translated into potent antitumor effects against TC-1 tumor cells.
134 16200349 These strategies include the use of the sorting signal of lysosome-associated membrane protein (LAMP-1), Mycobacterium tuberculosis heat shock protein 70 (HSP70), calreticulin (CRT) and herpes simplex virus type 1 (HSV-1) VP22 proteins.
135 16200349 In the current study, we have characterized DNA vaccines employing these intracellular targeting or intercellular spreading strategies targeting HPV-16 E6 for their ability to generate E6-specific CD8+ T cell immune responses and antitumor effects against an E6-expressing tumor cell line, TC-1, in C57BL/6 mice.
136 16200349 We found that all the intracellular targeting strategies (CRT, LAMP-1, HSP70) as well as the intercellular spreading strategy (VP22) were able to enhance E6 DNA vaccine potency, although the orientation of HSP70 linked to E6 antigen in the E6 DNA vaccine appears to be important for the HSP70 strategy to work.
137 16200349 The enhanced E6-specific CD8+ T cell immune response in vaccinated mice also translated into potent antitumor effects against TC-1 tumor cells.
138 16522814 We found that while SIV-specific T-cell responses are detectable in the majority of animals, their magnitude and breadth are, in fact, lower than what has been described in HIV-infected humans, both in terms of cytokine production (ie, IFN-gamma, TNF-alpha, and IL-2) and degranulation (ie, CD107a expression).
139 16844231 It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8(+) T cells, as well as to MHC class II-restricted CD4(+) T cells.
140 16844231 In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4(+) and CD8(+) T cells, compared with DC-E7 and DC-No insert.
141 16844231 More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-E7.
142 16844231 It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8(+) T cells, as well as to MHC class II-restricted CD4(+) T cells.
143 16844231 In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4(+) and CD8(+) T cells, compared with DC-E7 and DC-No insert.
144 16844231 More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-E7.
145 16844231 It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8(+) T cells, as well as to MHC class II-restricted CD4(+) T cells.
146 16844231 In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4(+) and CD8(+) T cells, compared with DC-E7 and DC-No insert.
147 16844231 More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-E7.
148 16972884 Interestingly, LAMP-1 immunoreactivity has little correlation with phosphorylated tau deposition and neurofibrillary tangles (NFTs), as neurones with NFTs were rarely LAMP-1 immunoreactive.
149 16972884 Finally, LAMP-1 occurred in microglia and multinucleated giant cells in one AD case in whom amyloid burden was cleared following betaA-peptide immunization.
150 16972884 Interestingly, LAMP-1 immunoreactivity has little correlation with phosphorylated tau deposition and neurofibrillary tangles (NFTs), as neurones with NFTs were rarely LAMP-1 immunoreactive.
151 16972884 Finally, LAMP-1 occurred in microglia and multinucleated giant cells in one AD case in whom amyloid burden was cleared following betaA-peptide immunization.
152 17158960 We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1beta, and surface mobilization of the degranulation marker CD107a by CD4+ T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes.
153 17158960 Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4+ T cell maturation.
154 17158960 Salient features of this profile were: (a) the simultaneous production of MIP-1beta, TNF-alpha, and IFN-gamma in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes.
155 17158960 Thus, mature CMV-specific CD4+ T cells exhibit distinct functional properties reminiscent of antiviral CD8+ T lymphocytes.
156 17158960 We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1beta, and surface mobilization of the degranulation marker CD107a by CD4+ T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes.
157 17158960 Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4+ T cell maturation.
158 17158960 Salient features of this profile were: (a) the simultaneous production of MIP-1beta, TNF-alpha, and IFN-gamma in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes.
159 17158960 Thus, mature CMV-specific CD4+ T cells exhibit distinct functional properties reminiscent of antiviral CD8+ T lymphocytes.
160 17188256 Induction of primary anti-HIV CD4 and CD8 T cell responses by dendritic cells transduced with self-inactivating lentiviral vectors.
161 17188256 In this study, we demonstrate that a minimal self-inactivating (SIN) lentiviral vector (LV) that does not encode any human immunodeficiency virus (HIV) genes is able to induce HIV-specific CD4 and CD8 T cell responses after transduction of dendritic cells (DCs).
162 17188256 The LV-DC-primed T cells displayed HIV-specific lytic degranulation, as illustrated by acquisition of CD107a/b expression on the cell surface and up-regulation of active caspase 3.
163 17188256 These results demonstrate that DCs transduced with the minimal SIN-LV can efficiently induce HIV-specific CD4 and CD8 T cell responses.
164 17230516 Enhancing dendritic cell vaccine potency by combining a BAK/BAX siRNA-mediated antiapoptotic strategy to prolong dendritic cell life with an intracellular strategy to target antigen to lysosomal compartments.
165 17230516 We show that small interfering RNA-targeting Bak and Bax proteins can be used to allow transfected DCs to resist being killed by T cells.
166 17230516 DCs expressing intact E7 or Sig/E7/LAMP-1 became resistant to attack by CD8+ T cells after transfection with BAK/BAX siRNA, leading to enhanced E7-specific T cell activation in vitro and in vivo.
167 17230516 More importantly, vaccination with E7-presenting DCs transfected with BAK/BAX siRNA generated a strong therapeutic effect against an E7-expressing tumor in vaccinated mice, compared with DCs transfected with control siRNA.
168 17589432 Synthetic melanoma-associated antigen MART1 mRNA was formulated with a polyethylene glycol (PEG)ylated derivative of histidylated polylysine and L-histidine-(N,N-di-n-hexadecylamine)ethylamide liposomes (termed histidylated lipopolyplexes).
169 17589432 MART1 mRNA lipopolyplexes elicited a cellular immune response characterized by the production of interferon-gamma and the induction of cytotoxic T lymphocytes.
170 17589432 Finally, the anti-B16 response was enhanced using a formulation containing both MART1 mRNA and MART1-LAMP1 mRNA encoding the antigen targeted to the major histocompatibility complex class II compartments by the lysosomal sorting signal of LAMP1 protein.
171 17615585 Robust CD4+ and CD8+ T cell responses to SIV using mRNA-transfected DC expressing autologous viral Ag.
172 17615585 Enhanced CD4+ T cell responses were stimulated when Gag was redirected into the lysosomal pathway via the targeting signal derived from lysosome-associated membrane protein-1 (LAMP-1).
173 17615585 Rhesus DC transfected with lysosome-targeted gag encoding an escape mutation in an immunodominant CTL epitope stimulated CD4+ and CD8+ T cell responses of almost equivalent magnitude directed towards undefined epitopes outside of the mutated region.
174 18097044 HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D.
175 18097044 However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date.
176 18097044 In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes.
177 18097044 Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286 epitopes.
178 18097044 Lastly, CD8+ T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2.
179 18192109 The patient received weekly intradermal injections of an HLA-A*2402-restricted 9-mer WT1 peptide emulsified with Montanide ISA 51 adjuvant for 12 weeks and achieved a minimal response according to European Group for Blood and Marrow Transplantation criteria without experiencing systemic adverse effects.
180 18192109 As for immunologic parameters, the frequency of WT1 tetramer-positive cells among CD8+ T-cells, which was higher than in healthy donors, temporarily decreased at weeks 4 and 8 but increased at week 12, whereas the frequency of WT1 peptide-responding CD107a/b+ cells among WT1 tetramer-positive T-cells increased from 27.0% to 38.6% after the vaccination.
181 18524823 The samples were tested using a statistically qualified nine-color intracellular cytokine staining assay measuring interleukin-2 (IL-2), tumor necrosis factor alpha, macrophage inflammatory protein 1beta, and gamma interferon production and expression of CD107a.
182 18524823 Both vaccine regimens induced CD4(+) and CD8(+) HIV gag-specific T-cell responses which variably expressed several intracellular markers.
183 18524823 Several trends were observed in which the frequencies of HIV-1-specific CD4(+) T cells and IL-2 production from antigen-specific CD8(+) T cells in the DNA/Ad5 cohort were more pronounced than in the Ad5/Ad5 cohort.
184 18566379 Identification of a novel immunogenic HLA-A*0201-binding epitope of HER-2/neu with potent antitumor properties.
185 18566379 By applying prediction algorithms for MHC class I ligands and proteosomal cleavages, in this study, we describe the identification of HER-2/neu decamer LIAHNQVRQV spanning residues 85-94 (HER-2(10(85))).
186 18566379 This peptide was immunogenic in HLA-A2.1 transgenic (HHD) mice inducing peptide-specific CTL, which responded to tumor cell lines of various origin coexpressing human HER-2/neu and HLA-A2.1.
187 18566379 Five of sixteen HER-2/neu+ HLA-A2.1+ breast cancer patients analyzed had HER-2(10(85))-reactive T cells ranging from 0.35-0.70% of CD8+ T cells.
188 18566379 Depletion of T regulatory cells from PBMC enabled the rapid expansion of HLA-A2.1/HER-2(10(85))pentamer+/CD8+ cells (PENT+/CD8+), whereas significantly lower numbers of CTL could be generated from unfractionated PBMC.
189 18566379 HER-2(10(85))-specific human CTL recognized the HER-2/neu+ HLA-A2.1+ tumor cell line SKBR3.A2, as determined by IFN-gamma intracellular staining and in the high sensitivity CD107alpha degranulation assay.
190 18566379 These data demonstrate that HER-2(10(85)) is an immunogenic peptide, capable of eliciting CD8-mediated responses in vitro and in vivo, providing the platform for further exploitation of HER-2(10(85)) as a possible target for anticancer immunotherapy.
191 18593941 Applying cryosurgery as an instant in situ tumor destruction technique, we now show that timing of CpG administration crucially affects colocalization of antigen and CpG within EEA-1(+) and LAMP-1(+) compartments within dendritic cells in vivo.
192 18713944 Here, we show that nonobese diabetic severe combined immunodeficiency (NOD/SCID) beta(2) microglobulin(-/-) mice, engrafted with human CD34+ hematopoietic progenitors and further reconstituted with T cells, can mount specific immune responses against influenza virus vaccines.
193 18713944 On ex vivo exposure to influenza antigens, antigen-specific CD8+ T cells produce IFN-gamma and express cell-surface CD107a.
194 18813797 After incubation with rec(IL-2) infected tumor cells, T cells showed increased expression of the activation marker CD69 and produced increased amounts of IFNgamma when compared to T cells co-incubated with rec(-) infected tumor cells.
195 18813797 CD8 T cells incubated with rec(IL-2) infected tumor cells showed upregulation of perforin, cell surface exposure of the degranulation marker CD107a and increased anti-tumor cytotoxic activity.
196 18813797 Purified T cells from lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients could be stimulated to secrete IFNgamma in an ELISPOT assay upon 40 h of stimulation with rec(IL-2) infected autologous tumor cells [ATV-rec(IL-2)] but not upon stimulation with rec(IL-2) infected allogeneic U937 tumor cells.
197 18832706 CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001).
198 18832706 Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the mild-moderate group.
199 19130551 These targeting signals, namely, lysosome-associated membrane protein 1 (LAMP1), tissue plasminogen activator (TPA) and ubiquitin, encoded various forms of PA viz. lysosomal, secreted and cytosolic, respectively.
200 19130551 Examination of IgG subclass distribution arising as a result of DNA vaccination indicated a higher IgG1:IgG2a ratio whenever the groups were immunized with chimeras bearing TPA, LAMP1 signals alone or when combined together.
201 19130551 These targeting signals, namely, lysosome-associated membrane protein 1 (LAMP1), tissue plasminogen activator (TPA) and ubiquitin, encoded various forms of PA viz. lysosomal, secreted and cytosolic, respectively.
202 19130551 Examination of IgG subclass distribution arising as a result of DNA vaccination indicated a higher IgG1:IgG2a ratio whenever the groups were immunized with chimeras bearing TPA, LAMP1 signals alone or when combined together.
203 19201387 Peptide-based vaccines, one of several anti-tumor immunization strategies currently under investigation, can elicit both MHC Class I-restricted (CD8(+)) and Class II-restricted (CD4(+)) responses.
204 19201387 We have tested overlapping synthetic peptides (OSP) representing a tumor antigen as a novel approach that bypasses the need for epitope mapping, since OSP contain all possible epitopes for both CD8(+) and CD4(+) T cells.
205 19201387 Here we report that vaccination of inbred and outbred mice with OSP representing tumor protein D52 (TPD52-OSP), a potential tumor antigen target for immunotherapy against breast, prostate, and ovarian cancer, was safe and induced specific CD8(+) and CD4(+) T-cell responses, as demonstrated by development of specific cytotoxic T cell (CTL) activity, proliferative responses, interferon (IFN)-gamma production and CD107a/b expression in all mice tested.
206 19342665 S221 did not replicate well in wild-type mice, but did induce a CD8(+) T cell response, whereas viral replication and a robust CD8(+) T cell response were observed after infection of IFN-alpha/betaR(-/-) mice.
207 19342665 Depletion of CD8(+) T cells from IFN-alpha/betaR(-/-) mice before infection resulted in significantly higher viral loads compared with undepleted mice.
208 19342665 Mapping the specificity of the CD8(+) T cell response led to the identification of 12 epitopes derived from 6 of the 10 DENV proteins, with a similar immunodominance hierarchy observed in wild-type and IFN-alpha/betaR(-/-) mice.
209 19342665 DENV-specific CD8(+) T cells produced IFN-gamma, TNF-alpha, expressed cell surface CD107a, and exhibited cytotoxic activity in vivo.
210 19357176 Here we show that a primary CD8(+) T-cell response can be induced by HIV-1 peptide-loaded DC derived from blood monocytes of HIV-1-negative adults and neonates (moDC) and by Langerhans cells (LC) and interstitial, dermal-intestinal DC (idDC) derived from CD34(+) stem cells of neonatal cord blood.
211 19357176 Optimal priming of single-cell gamma interferon (IFN-gamma) production by CD8(+) T cells required CD4(+) T cells and was broadly directed to multiple regions of Gag, Env, and Nef that corresponded to known and predicted major histocompatibility complex class I epitopes.
212 19357176 Polyfunctional CD8(+) T-cell responses, defined as single-cell production of more than one cytokine (IFN-gamma, interleukin 2, or tumor necrosis factor alpha), chemokine (macrophage inhibitory factor 1beta), or cytotoxic degranulation marker CD107a, were primed by moDC, LC, and idDC to HIV-1 Gag and reverse transcriptase epitopes, as well as to Epstein-Barr virus and influenza A virus epitopes.
213 19532140 We show that a single vaccination using an optimized gene delivery generates (i) high and consistent protein expression in vivo, (ii) cytotoxic antigen-specific T cells expressing both IFNgamma and CD107a (lysosomal-associated membrane protein 1).
214 19651871 Perforin and gamma interferon expression are required for CD4+ and CD8+ T-cell-dependent protective immunity against a human parasite, Trypanosoma cruzi, elicited by heterologous plasmid DNA prime-recombinant adenovirus 5 boost vaccination.
215 19651871 A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4(+) and CD8(+) T-cell-mediated protective immunity against intracellular pathogens.
216 19651871 We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4(+) and CD8(+) T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi.
217 19651871 In spite of a normal numeric expansion, specific CD8(+) T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-gamma or IFN-gamma/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1.
218 19965687 DNA vaccination with all-trans retinoic acid treatment induces long-term survival and elicits specific immune responses requiring CD4+ and CD8+ T-cell activation in an acute promyelocytic leukemia mouse model.
219 19965687 Depletion of CD4(+) or CD8(+) cells abolished this effect.
220 19965687 CD4(+) depletions of long-term survivors resulted in relapse and death within 3 months, thus demonstrating the need of both CD4(+) and CD8(+) subsets for the generation of DNA-driven antileukemic immune responses and underscoring a crucial role of CD4(+) cells in the maintenance of durable remissions.
221 19965687 Sorted APL-specific CD8(+)CD107a(+) T cells showed an increase of antileukemic activity.
222 19965687 Effectors from ATRA + DNA-treated mice were shown to secrete interferon-gamma when stimulated with either APL cells or peptides from the promyelocytic leukemia-RARalpha vaccine-derived sequences as detected by ELISpot assays.
223 20220777 CD8(+) T cells primed with the RHAMM-derived epitope R3, which is restricted by human leukocyte antigen (HLA)-A2, effectively lyse RHAMM(+) CLL cells.
224 20220777 Six HLA-A2(+) CLL patients were vaccinated four times at biweekly intervals with the R3 peptide (ILSLELMKL; 300 microg per dose) emulsified in incomplete Freund's adjuvant; granulocyte-macrophage colony stimulating factor (100 microg per dose) was administered concomitantly.
225 20220777 In patients with clinical responses, we found increased frequencies of R3-specific CD8(+) T cells that expressed high levels of CD107a and produced both interferon-gamma and granzyme B in response to antigen challenge.
226 20220777 Thus peptide vaccination in six CLL patients was safe and could elicit to some extent specific CD8(+) T-cell responses against the tumor antigen RHAMM.
227 20445343 Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy.
228 20445343 Previous reports demonstrate that cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibodies promote T-cell activation and render T effector cells resistant to T regulatory cells (Tregs) whereas programmed death receptor-1 (PD-1)/PD-L1 blockade results in loss of peripheral tolerance.
229 20445343 Herein, we explored single or combined antibody blockade of CTLA-4 and PD-1 alone or combined with the toll-like receptor agonists CpG or bacillus Calmette-Guérin for treatment of murine experimental bladder cancer.
230 20445343 However, elevated levels of circulating CD107a expressing CD8 T cells were found in the aCTLA-4 plus aPD-1 group.
231 20445343 CpG plus aCTLA-4 or aPD-1 increased the numbers of circulating tumor-specific CD107a expressing CD8 T cells as well as activated (CD25FoxP3-) CD4 splenocytes.
232 20445343 Thus, the combination of CpG with CTLA-4 or PD-1 blockade improved long-term survival and led to increased levels of tumor-reactive T cells and reduced numbers of Tregs at the tumor site.
233 20445343 Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy.
234 20445343 Previous reports demonstrate that cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibodies promote T-cell activation and render T effector cells resistant to T regulatory cells (Tregs) whereas programmed death receptor-1 (PD-1)/PD-L1 blockade results in loss of peripheral tolerance.
235 20445343 Herein, we explored single or combined antibody blockade of CTLA-4 and PD-1 alone or combined with the toll-like receptor agonists CpG or bacillus Calmette-Guérin for treatment of murine experimental bladder cancer.
236 20445343 However, elevated levels of circulating CD107a expressing CD8 T cells were found in the aCTLA-4 plus aPD-1 group.
237 20445343 CpG plus aCTLA-4 or aPD-1 increased the numbers of circulating tumor-specific CD107a expressing CD8 T cells as well as activated (CD25FoxP3-) CD4 splenocytes.
238 20445343 Thus, the combination of CpG with CTLA-4 or PD-1 blockade improved long-term survival and led to increased levels of tumor-reactive T cells and reduced numbers of Tregs at the tumor site.
239 20660136 Because of the potential importance of HLA-E-restricted CD8(+) responses in resistance to Salmonella infection, we characterized these responses and investigated their kinetics of appearance and persistence in volunteers immunized orally with the licensed attenuated Ty21a strain typhoid vaccine.
240 20660136 An ex vivo multicolor staining panel including antibodies to CD107a and -b, interleukin-2, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) was used to functionally assess memory T-cell subsets by flow cytometry.
241 20660136 The majority of HLA-E-restricted CD8(+) cells 28 to 56 days after immunization coexpressed CD107, IFN-gamma, and TNF-alpha, showing characteristic features of multifunctional T cells.
242 20660136 In summary, the multifunctionality and longevity of the HLA-E-restricted CD8 responses observed in this study highlight their significance in adaptive immunity to S.
243 20660136 Finally, this is the first demonstration, in either animals or humans, of the presence of long-term multifunctional HLA-E-restricted CD8(+) cells after immunization.
244 20709007 CD8+ T cell response in HLA-A*0201 transgenic mice is elicited by epitopes from SARS-CoV S protein.
245 20709007 Results showed that peptide-specific CD8(+) T cells secreted IFN-γ, TNF-α and IL-2 and expressed CD107a/b on cell surface.
246 20709007 IFN-γ(+)CD8(+) T cells and CD107a/b(+)CD8(+) T cells distributed throughout the lymphoid and non-lymphoid tissues, but the frequency of peptide-specific CD8(+) T cells was higher in lungs than in spleens and lymph nodes.
247 20709007 Most of the HLA-A*0201 restricted peptide-specific CD8(+) T cells represented a memory subset with CD45RB(high) and CD62L(low).
248 20709007 Taken together, these data demonstrate that immunization with SARS S DNA and HLA-A*0201 restricted peptides can elicit antigen-specific CD8(+) T cell immune responses which may have a significant implication in the long-term protection.
249 20709007 CD8+ T cell response in HLA-A*0201 transgenic mice is elicited by epitopes from SARS-CoV S protein.
250 20709007 Results showed that peptide-specific CD8(+) T cells secreted IFN-γ, TNF-α and IL-2 and expressed CD107a/b on cell surface.
251 20709007 IFN-γ(+)CD8(+) T cells and CD107a/b(+)CD8(+) T cells distributed throughout the lymphoid and non-lymphoid tissues, but the frequency of peptide-specific CD8(+) T cells was higher in lungs than in spleens and lymph nodes.
252 20709007 Most of the HLA-A*0201 restricted peptide-specific CD8(+) T cells represented a memory subset with CD45RB(high) and CD62L(low).
253 20709007 Taken together, these data demonstrate that immunization with SARS S DNA and HLA-A*0201 restricted peptides can elicit antigen-specific CD8(+) T cell immune responses which may have a significant implication in the long-term protection.
254 20719985 These new HHV-8 epitopes activated monofunctional and polyfunctional CD8(+) T cells that produced various combinations of gamma interferon, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1β, and cytotoxic degranulation marker CD107a in healthy HHV-8-seropositive individuals.
255 20719985 We were also able to detect HHV-8-specific CD8(+) T cells in peripheral blood samples using HLA A*0201 pentamer complexes for one gB epitope, one K8.1 epitope, two LANA-1 epitopes, and one K12 epitope.
256 20739505 Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8(+) T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells).
257 20739505 In the present report, we characterized some previously uncovered aspects concerning the induction of CD8(+) T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells.
258 20739505 Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4(+) T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8(+) T-cell responses.
259 20739505 Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8(+) T-cell responses, measured by intracellular gamma interferon (IFN-γ) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2D(b)-restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein.
260 20739505 In addition, coadministration of pgD-E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells.
261 21367979 P313-specific CD4(+) T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells.
262 21796616 However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients.
263 21796616 The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells.
264 21796616 Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways.
265 21856357 A detailed analysis of the cell-mediated immune responses by ICS showed the number of specific CD8(+) T cells expressing cytokines (IFN-γ, TNF-α, and IL-2) and granule-associated proteins (CD107a) was higher than that of specific CD4(+) T cells secreted by immune spleen cells upon restimulation in vitro with peptides.
266 21881953 Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques.
267 21881953 DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia.
268 21881953 DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β).
269 21881953 In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a.
270 21881953 Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic.
271 21881953 Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques.
272 21881953 DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia.
273 21881953 DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β).
274 21881953 In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a.
275 21881953 Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic.
276 21969597 Pulmonary immunization with NP-conjugated ovalbumin (NP-ova) with CpG induced a threefold enhancement of splenic antigen-specific CD8(+) T cells displaying increased CD107a expression and IFN-γ production compared with immunization with soluble (i.e., unconjugated) ova with CpG.
277 22080404 To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant.
278 22080404 Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups.
279 22080404 Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo.
280 22080404 In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers.
281 22345455 This assay assessed activation (gamma interferon [IFN-γ] production and/or CD107a expression) of KIR3DL1(+) and KIR3DL1(-) NK cells, from HLA-Bw4(+) and HLA-Bw4(-) HIV-positive and HIV-negative individuals, in response to autologous HIV-specific ADCC targets.
282 22345455 However, peripheral CD4(+) T-lymphocyte counts were not correlated with an anti-HIV ADCC functional advantage in educated KIR3DL1(+) NK cells.
283 22355381 The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation.
284 22355381 Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates.
285 22379065 The magnitude of IFN-γ-producing CD8(+) T-cell responses to CMV-specific peptides measured with the QuantiFERON-CMV assay correlated significantly (σ = 0.695; P = <0.001) with that of the total IFN-γ-producing CD8(+) T cells and dual-functional (IFN-γ/tumor necrosis factor alpha [TNF-α] [σ = 0.652; P = <0.001] and IFN-γ/CD107a [σ = 0.690; P = <0.001]) and trifunctional (IFN-γ/TNF-α/CD107a [σ = 0.679; P = >0.001]) CMV-specific CD8(+) T-cell responses, as quantitated by ICS.
286 22379065 In summary, the data indicated that the QuantiFERON-CMV assay is less sensitive than the ICS method for the detection of CMV-specific IFN-γ-producing CD8(+) T-cell responses in the allo-SCT setting.
287 22379065 Nevertheless, it allowed the estimation of the total and polyfunctional CMV-specific IFN-γ-producing CD8(+) T-cell responses in specimens that tested positive by both methods.
288 22412866 We hypothesized that this immunity depends on polyfunctional memory T cells, i.e., CD4(+) and/or CD8(+) T cells with the capability to simultaneously express several functional markers.
289 22412866 Significant differences were detected between either of the immune donor groups and naïve individuals for secreted levels of IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, MCP-1, and MIP-1β.
290 22412866 Expression of IFN-γ, MIP-1β, and CD107a by CD4(+)CD45RO(+) or CD8(+)CD45RO(+) T cells correlated to antigen concentrations.
291 22412866 Notably, IL-2- or TNF-α-secretion was low.
292 22508289 Furthermore, ex vivo polychromatic functional analysis of the CMV-specific T-cells from GBM patients revealed that large proportions of these cells were unable to produce multiple cytokines (macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF)α and interferon (IFN)γ) and displayed limited cytolytic function (CD107a mobilization) following stimulation with CMV peptide epitopes.
293 22529301 Intracellular cytokine staining confirmed that Env responses predominated (19 of 30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4(+) T cells, with the majority of responders producing both IL-2 and IFN-γ (12 of 19; 63%).
294 22529301 Proliferation assays revealed that HIV Ag-specific T cells were CD4(+), with the majority (80%) expressing CD107a.
295 22617838 VV-HIV- IFN-ε infection induced a rapid VV clearance in lung that correlated with (i) an elevated lung VV-specific CD8(+)CD107a(+)IFN-γ(+) population expressing activation markers CD69/CD103, (ii) enhanced lymphocyte recruitment to lung alveoli with reduced inflammation, and (iii) an heightened functional/cytotoxic CD8(+)CD4(+) T-cell subset (CD3(hi)CCR7(hi)CD62L(lo)) in lung lymph nodes.
296 22617838 Homing marker α4β7 and CCR9 analysis indicated that unlike other type I IFNs, IFN-ε could promote migration of antigen-specific CD8(+)T cells to the gut.
297 22927933 On the other hand, when adult mice were primed with BCG.HIVA(CAT) and boosted with MVA.HIVA.85A, HIV-1-specific CD8(+) T-cells producing IFN-γ, TNF-α, IL-2 and CD107a were induced.
298 23049876 Gag-specific IFN-γ ELISPOT, intracellular cytokine staining (ICS) (CD107a, IFN-γ, TNF-α and IL-2), pentamer staining and T-cell phenotyping were used to differentiate responses to inserts and vectors.
299 23239796 Higher levels of interleukin-13 (IL-13; 3,000 ± 1,000 pg/ml) in cultured PBMC supernatants and lower frequency of RSV F-specific CD107a(+) CD8(+) T cells (3.0% ± 1.6% versus 5.0% ± 1.6%) were measured in PBMC from elderly than young adults.
300 23271970 In the aged cohort, the CD8+ T cell compartment displayed a marked reduction in the frequency of naïve CD8+ T cells and increased frequencies of CD8+ T cells that expressed CD57 and lacked CD28, as previously described.
301 23271970 However, we did not observe an influence of age on either the frequency of virus-specific CD8+ T cells within the circulating pool nor their functionality (based on the production of IFNγ, TNFα, IL2, Granzyme B, Perforin and mobilization of CD107a).
302 23314272 T-cell immunogenicity was examined longitudinally by a flow cytometry (CD107a, IFNγ, TNFα, IL-2 and/or MIP1β expression) as well as IFNγ ELISPOT.
303 23314272 New CD4 and CD8 T-cell responses specific for one or more vaccine epitopes were induced in 10/10 vaccinees.
304 23326300 Elevated expression of CD69, CD44 and Ki67 on CD8(+) T cells revealed their state of activation and proliferation by NLGP.
305 23326300 Consistently higher expression of CD107a was also observed in CD8(+) T cells from tumors.
306 23326300 This is correlated with the increment of CD44(hi)CD62L(hi) central memory T cells.
307 23555672 C57BL/6 mice immunized with TcVac3 elicited a strong antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1); and a robust antigen- and Tc-specific CD8(+)T cell response with type-1 cytokine (IFN-γ(+)TNF-α>IL-4(+)IL-10) and cytolytic effector (CD8(+)CD107a(+)IFN-γ(+)Perforin(+)) phenotype.
308 23555672 Co-delivery of IL-12 and GMCSF cytokine adjuvants didn't enhance the TcVac3-induced resistance to T. cruzi.
309 23555672 In chronic phase, vaccinated/infected mice exhibited a significant decline (up to 70%) in IFN-γ(+)CD8(+)T cells, a predominance of immunoregulatory IL-10(+)/CD4(+)T and IL10(+)/CD8(+)T cells, and presented undetectable tissue parasitism, inflammatory infiltrate, and fibrosis in vaccinated/infected mice.
310 23637908 Analyzing the phenotype of CD8+ T cells obtained from spleen of vaccinated C3H/He mice we observed that heterologous prime-boost immunization protocol elicited more CD8+ T cells specific for the immunodominant epitope as well as a higher number of CD8+ T cells producing TNF-α and IFN-γ and a higher mobilization of surface marker CD107a.
311 23637967 Among participants with additional cryo-preserved PBMCs, HIV-specific CD8+ T cell immunity as indicated by increased expression of degranulation marker CD107a and macrophage inflammatory protein 1β (MIP1β) tended to be up-regulated following immunization with CPG 7909 compared with placebo as adjuvant.
312 23637967 Further, increasing proportion of HIV-specific CD107a and MIP1β-expressing CD8+ T cells were strongly correlated with decreasing proviral load.
313 23637967 Among participants with additional cryo-preserved PBMCs, HIV-specific CD8+ T cell immunity as indicated by increased expression of degranulation marker CD107a and macrophage inflammatory protein 1β (MIP1β) tended to be up-regulated following immunization with CPG 7909 compared with placebo as adjuvant.
314 23637967 Further, increasing proportion of HIV-specific CD107a and MIP1β-expressing CD8+ T cells were strongly correlated with decreasing proviral load.
315 23685781 In vitro experiments using mouse splenocytes showed that γδ T cells produce IFN-γ after treatment with PSK and have up-regulated expression of CD25, CD69, and CD107a.
316 23729440 Consistent with their specific receptor expression, skin DCs bound and internalized Env via C-type lectin receptors, whereas blood DC subsets, including CD1c(+) myeloid DCs, CD123(+) plasmacytoid DCs (PDCs), and CD141(+) DCs exhibited a restricted repertoire of C-type lectin receptors and relied on CD4 for uptake of Env.
317 23729440 Despite a generally poor capacity for Ag uptake compared with myeloid DCs, the high expression of CD4 on PDCs allowed them to bind and internalize Env very efficiently.
318 23729440 CD4-mediated uptake delivered Env to EEA1(+) endosomes that progressed to Lamp1(+) and MHC class II(+) lysosomes where internalized Env was degraded rapidly.
319 23731631 In addition, m8Δ/pSFJ/SIVGag was less pathogenic and elicited Gag-specific IFN-γ(+), CD107a(+), CD8(+) cells more efficiently than m8Δ/p7.5/SIVGag.
320 23894722 TLR3 agonists improve the immunostimulatory potential of cetuximab against EGFR+ head and neck cancer cells.
321 23894722 We investigated the effect of TLR3 agonists on cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against head and neck cancer (HNC) cells, as well as on dendritic cell (DC) maturation and cross-priming of epidermal growth factor receptor (EGFR)-specific CD8+ T cells.
322 23894722 The DC-mediated cross priming of EGFR-specific CD8+ T cells was monitored upon in vitro stimulation with tetramer-based flow cytometry.
323 23894722 The cytolytic activity of TLR3-stimulated NK cells differed among cells expressing different polymorphic variants of FcγRIIIa, and NK cells exposed to both poly-ICLC and cetuximab expressed higher levels of CD107a and granzyme B than their counterparts exposed to either stimulus alone.
324 23894722 Poly-ICLC plus cetuximab also induced a robust upregulation of CD80, CD83 and CD86 on the surface of DCs, a process that was partially NK-cell dependent.
325 23894722 Furthermore, DCs matured in these conditions exhibited improved cross-priming abilities, resulting in higher numbers of EGFR-specific CD8+ T cells.
326 23906886 Vacc-4x T cell responses were measured by proliferation (CFSE), INF-γ, CD107a, Granzyme B, Delayed-Type Hypersensitivity test (DTH) and cytokines and chemokines (Luminex).
327 23906886 At baseline, responders had higher CD8(+) T cell degranulation (p=0.05) and CD4(+) INF-γ production (p=0.01), whereas non-responders had higher production of proinflammatory TNF-α, IL-1α and IL-1ß (p<0.045) and regulatory IL-10 (p=0.07).
328 23906886 Notably, IL-10 and TGF-ß mediated downregulation of Vacc-4x-specific CD8(+) T cell proliferation increased only in non-responders (p<0.001).
329 23906886 Downregulation during the study correlated to higher PD-1 expression on Vacc-4x-specific CD8(+) T cells (r=0.44, p=0.037), but was inversely correlated to changes in Vacc4x-specific CD8(+) T cell proliferation (r=-0.52, p=0.012).
330 23966552 The CD3(+) CD4(-) CD8(hi) T cell population was the first and major source of CSFV-specific IFN-γ.
331 23966552 A proportion of these cells showed evidence for cytotoxicity, as evidenced by CD107a mobilization, and coexpressed tumor necrosis factor alpha (TNF-α).
332 23966552 While virus-specific CD4 T cell (CD3(+) CD4(+) CD8α(+)) responses were detected, the dominant response was again from the CD8 T cell population, with the highest numbers of these cells being detected 14 and 7 days after the primary and secondary challenges, respectively.
333 23966552 These CD8 T cells were further characterized as CD44(hi) CD62L(-) and expressed variable levels of CD25 and CD27, indicative of a mixed effector and effector memory phenotype.
334 23966552 The majority of virus-specific IFN-γ(+) CD8 T cells isolated at the peaks of the response after each challenge displayed CD107a on their surface, and subpopulations that coexpressed TNF-α and interleukin 2 (IL-2) were identified.
335 23966552 The CD3(+) CD4(-) CD8(hi) T cell population was the first and major source of CSFV-specific IFN-γ.
336 23966552 A proportion of these cells showed evidence for cytotoxicity, as evidenced by CD107a mobilization, and coexpressed tumor necrosis factor alpha (TNF-α).
337 23966552 While virus-specific CD4 T cell (CD3(+) CD4(+) CD8α(+)) responses were detected, the dominant response was again from the CD8 T cell population, with the highest numbers of these cells being detected 14 and 7 days after the primary and secondary challenges, respectively.
338 23966552 These CD8 T cells were further characterized as CD44(hi) CD62L(-) and expressed variable levels of CD25 and CD27, indicative of a mixed effector and effector memory phenotype.
339 23966552 The majority of virus-specific IFN-γ(+) CD8 T cells isolated at the peaks of the response after each challenge displayed CD107a on their surface, and subpopulations that coexpressed TNF-α and interleukin 2 (IL-2) were identified.
340 23980113 Here, we have further characterized vaccine-induced changes in the CD8(+) T cell phenotype and demonstrated significant upregulation of CD11c on CD3(+) CD8b(+) T cells in the liver, spleen, and peripheral blood.
341 23980113 CD11c(+) CD8(+) T cells are predominantly CD11a(hi) CD44(hi) CD62L(-), indicative of antigen-experienced effector cells.
342 23980113 Following in vitro restimulation with malaria-infected hepatocytes, CD11c(+) CD8(+) T cells expressed inflammatory cytokines and cytotoxicity markers, including IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), perforin, and CD107a.
343 23980113 CD11c(-) CD8(+) T cells, on the other hand, expressed negligible amounts of all inflammatory cytokines and cytotoxicity markers tested, indicating that CD11c marks multifunctional effector CD8(+) T cells.
344 23980113 Coculture of CD11c(+), but not CD11c(-), CD8(+) T cells with sporozoite-infected primary hepatocytes significantly inhibited liver-stage parasite development.
345 23980113 Tetramer staining for the immunodominant circumsporozoite protein (CSP)-specific CD8(+) T cell epitope demonstrated that approximately two-thirds of CSP-specific cells expressed CD11c at the peak of the CD11c(+) CD8(+) T cell response, but CD11c expression was lost as the CD8(+) T cells entered the memory phase.
346 23980113 Further analyses showed that CD11c(+) CD8(+) T cells are primarily KLRG1(+) CD127(-) terminal effectors, whereas all KLRG1(-) CD127(+) memory precursor effector cells are CD11c(-) CD8(+) T cells.
347 24101547 Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.
348 24101547 In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence.
349 24101547 In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569.
350 24101547 In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449).
351 24101547 ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals.
352 24101547 Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease.
353 24101547 Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.
354 24101547 In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence.
355 24101547 In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569.
356 24101547 In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449).
357 24101547 ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals.
358 24101547 Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease.
359 24291199 By analyzing the differentiation state of IFN-γ-secreting CD8(+) T cells, we found a CCR7(-)CD45RA(-)CD28(+int)/CD28(-) profile (>85%) belonging to a subset of intermediate-differentiated effector T cells for HIV, FLU, and EBV.
360 24291199 The percentage of single IFN-γ T cell producers in response to HIV was 62% of the total of secreting T cells compared with 35% for FLU and EBV, dual and triple (IFN-γ/IL-2/CD107a) T cell producers could also be detected but at lower levels (8% compared with 37%).
361 24349220 Human CD8+ T cells from TB pleurisy respond to four immunodominant epitopes in Mtb CFP10 restricted by HLA-B alleles.
362 24349220 The epitope-specific CD8(+) T cells displayed effector or effector memory phenotypes and could upregulate the expression of CD107a/b upon antigen stimulation.
363 24349220 As judged from HLA-typing results and using bioinformatics technology for prediction of MHC binding affinity, we found that the epitope-specific CD8(+) T cells are all restricted by HLA-B alleles.
364 24376799 Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-α in addition to IFN-γ.
365 24530576 Our data suggests that stimulation with VACV triggers a cytotoxic response by NK cells marked by an increase of NCRs: NKp30, NKp44, and NKp46 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals.
366 24530576 We demonstrated that stimulation with VACV downregulates the percentage of expression of Perforin, Granzyme A, and CD107a, but upregulate CD94 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals.
367 24530576 Our data suggest that the expression of NCRs NKp30, NKp44, NKp46 and cytokines by NK cells are important in the innate response against VACV.
368 24709642 Peptide specific CD8+ human T cell lines from peripheral blood lymphocytes were generated from a HLA-A*02+ donor.
369 24709642 High frequencies of peptide specific CD8+ T cell responses were elicited in mice by DNA vaccination with ICP27, VP22 and VP13/14, as demonstrated by CD107a mobilization.
370 24777680 When delivered by electroporation, phTERT elicited strong, broad hTERT-specific CD8 T-cell responses including induction of T cells expressing CD107a, IFN-γ, and TNF-α in mice.
371 24905579 A better understanding of the role of CD4+ and CD8+ T cells, which are both important to TB protection, is essential to unravel the mechanisms of protection and to identify the key antigens seen by these T cells.
372 24905579 An Rv2034-specific CD4+ T-cell clone expressed the Th1 markers T-bet, IFN-γ, TNF-α, IL-2 and the cytotoxicity related markers granzyme B and CD107a as measured by flow cytometry.
373 24935722 A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients.
374 24935722 Our results demonstrate that MP-CTLs generated from SMM patients' T cells show effective anti-MM responses including CD137 (4-1BB) upregulation, CTL proliferation, interferon-γ production and degranulation (CD107a) in an HLA-A2-restricted and peptide-specific manner.
375 24935722 Phenotypically, we observed increased total CD3(+)CD8(+) T cells (>80%) and cellular activation (CD69(+)) within the memory SMM MP-CTL (CD45RO(+)/CD3(+)CD8(+)) subset after repeated multipeptide stimulation.
376 24995010 A dominant effector memory T (TEM) phenotype was observed in gastric LPMC CD4(+) and CD8(+) T cells in all age groups.
377 24995010 We then evaluated whether these cells represented a population of gastric tissue-resident memory T (TRM) cells by assessing expression of CD103 and CD69.
378 24995010 The vast majority of gastric LPMC CD8(+) T cells either co-expressed CD103/CD69 (>70%) or expressed CD103 alone (~20%).
379 24995010 Gastric LPMC CD4(+) T cells also either co-expressed CD103/CD69 (>35%) or expressed at least one of these markers.
380 24995010 Thus, gastric LPMC CD8(+) and CD4(+) T cells had the characteristics of TRM cells.
381 24995010 Gastric CD8(+) and CD4(+) TRM cells produced multiple cytokines (IFN-γ, IL-2, TNF-α, IL-17A, MIP-1β) and up-regulated CD107a upon stimulation.
382 24995010 Furthermore, gastric CD8(+) TRM and CD4(+) TRM cells demonstrated differences in the frequency, susceptibility to activation, and cytokine/multi-cytokine production profiles among the age groups.
383 25275131 Vaccine-induced CD107a+ CD4+ T cells are resistant to depletion following AIDS virus infection.
384 25424943 In addition, multiparametric flow cytometry detected HCV-specific CD4+ and CD8+ T cell responses by intracellular cytokine staining and detected HCV-specific CD107a+/GrzB+ CD8+ T cells indicating an antigen specific cytolytic response 2 weeks PIR compared with baseline measurements.
385 25617628 Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)γ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase.
386 25617628 Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels.
387 25786238 Here we described possible strategies for rational design of T-cell vaccine capable to induce high levels of both CD4+ and CD8+ T- cell responses.
388 25786238 We developed artificial HIV-1 polyepitope T-cell immunogens based on the conserved natural CD8+ and CD4+ T cell epitopes from different HIV-1 strains and restricted by the most frequent major human leukocyte antigen (HLA) alleles.
389 25786238 Designed immunogens contain optimized core polyepitope sequence and additional "signal" sequences which increase epitope processing and presentation to CD8+ and CD4+ T-lymphocytes: N-terminal ubiquitin, N-terminal signal peptide and C-terminal tyrosine motif of LAMP-1 protein.
390 25786238 All designed immunogens were able to elicit HIV-specific CD4+ and CD8+ T cell responses following immunization.
391 25786238 Attachment of either ubiquitin or ER-signal/LAMP-1 sequences increased both CD4+ and CD8+ mediated HIV-specific T cell responses in comparison with polyepitope immunogen without any additional signal sequences.
392 25786238 Moreover, TCI-N3 polyepitope immunogen with ubiquitin generated highest magnitude of HIV-specific CD4+ and CD8+ T cell responses in our study.
393 25786238 Here we described possible strategies for rational design of T-cell vaccine capable to induce high levels of both CD4+ and CD8+ T- cell responses.
394 25786238 We developed artificial HIV-1 polyepitope T-cell immunogens based on the conserved natural CD8+ and CD4+ T cell epitopes from different HIV-1 strains and restricted by the most frequent major human leukocyte antigen (HLA) alleles.
395 25786238 Designed immunogens contain optimized core polyepitope sequence and additional "signal" sequences which increase epitope processing and presentation to CD8+ and CD4+ T-lymphocytes: N-terminal ubiquitin, N-terminal signal peptide and C-terminal tyrosine motif of LAMP-1 protein.
396 25786238 All designed immunogens were able to elicit HIV-specific CD4+ and CD8+ T cell responses following immunization.
397 25786238 Attachment of either ubiquitin or ER-signal/LAMP-1 sequences increased both CD4+ and CD8+ mediated HIV-specific T cell responses in comparison with polyepitope immunogen without any additional signal sequences.
398 25786238 Moreover, TCI-N3 polyepitope immunogen with ubiquitin generated highest magnitude of HIV-specific CD4+ and CD8+ T cell responses in our study.
399 25844718 Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.
400 25844718 Furthermore, evaluation of overlapping SIV p24 peptide sequences identified conserved epitope(s) on the Fp14/Hp15-counterpart of SIV, Sp14, but none on Fp9-counterpart of SIV, Sp9.
401 25844718 Intracellular staining analysis for cytotoxins and phenotyping for CD107a determined that peptide epitopes from Fp9 and Fp14 pools induced cytotoxic T lymphocyte-associated molecules including perforin, granzyme B, granzyme A, and/or expression of CD107a.
402 25872480 These CD8+ T-cell responses were largely mediated by MF cells coproducing interferon-γ and macrophage inflammatory protein-1β and expressing CD107a with or without tumor necrosis factor-α.
403 25875109 The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments.
404 25941601 XBP1-CTL were enriched withCD45RO+ memory CTL, which showed high expression of critical T cell markers (CD28, ICOS, CD69, CD40L), cell proliferation and antitumor activities as compared to CD45RO- non-memory CTL.
405 25941601 The effector memory (EM: CD45RO+CCR7-) subset had the highest level of cell proliferation while the central memory (CM: CD45RO+CCR7+) subset demonstrated enhanced functional activities (CD107a degranulation, IFNγ/IL-2 production) upon recognition of the respective tumor cells.
406 25941601 The highest frequencies of IFNγ or granzyme B producing cells were detected within CM XBP1-CTL subset that were either Tbet+ or Eomes+ in responding to the tumor cells.These results demonstrate the immunotherapeutic potential of a cocktail of immunogenic HLA-A2 specific heteroclitic XBP1 US184-192 and heteroclictic XBP1 SP367-375 peptides to induce CD3+CD8+ CTL enriched for CM and EM cells with specific antitumor activities against a variety of solid tumors.
407 26015961 Polyfunctional HIV-1-specific CD8+ T cells, which produce interferon-γ and tumor necrosis factor-α and express the degranulation marker CD107a, were induced.
408 26091502 Low expression of activation marker CD69 and chemokine receptors CCR5 and CXCR3 on memory T cells after 2009 H1N1 influenza A antigen stimulation in vitro following H1N1 vaccination of HIV-infected individuals.
409 26091502 Cells collected just prior to vaccination and at 1 and 3 months afterwards were stimulated in vitro with dialyzed vaccine antigen and assayed by flow cytometry for cytokines TNF-α, IFN-γ, IL-2, and IL-10, for degranulation marker CD107a, as well as phenotypes of memory T-cell subpopulations.
410 26091502 However, by 3 months post-vaccination, in vitro antigen stimulation of peripheral blood mononuclear cells induced greater expansion in controls of both CD4 and CD8 central memory and effector memory T cells, as well as higher expression of the activation marker CD69 and chemokine receptors CCR5 and CXCR3 than in HIV+ subjects.
411 26091502 We concluded CD4+ and CD8+ memory T cells produce cytokines at comparable levels in both groups, whereas the expression after in vitro stimulation of molecules critical for cell migration to infection sites are lower in the HIV+ than in comparable controls.
412 26232347 We found no significant differences in the increase of cytokines-producing and CD107a-expressing CD8+ T cells or CD8+ memory T cells in response to pooled conserved epitopes stimulation in vitro between children with different serologic responses to the vaccine at all time points of the study.
413 26272673 Identification of CD8 T cell epitopes in VP2 and NS1 proteins of African horse sickness virus in IFNAR(-/-) mice.
414 26272673 Previous work in our laboratory showed the presence of AHSV-specific CD8(+) T cells in mice immunized with recombinant Modified Vaccinia Ankara (rMVA) expressing VP2 and NS1 proteins.
415 26272673 In the present work, we selected potential CD8 T cell epitopes (MHC-class I binding peptides) for the 129 mouse strain from the VP2 and NS1 proteins of AHSV-4, using a combination of four epitope prediction algorithms (SYFPEITHI, BYMAS, NetMHC I and NetMHCpan).
416 26272673 In addition, these three MHC-class I-binding peptides induced the expression of CD107a in CD8(+) T cells, an indirect marker of cytotoxic activity.
417 26450377 Liver CD3 + CD8 T cells can further be divided into subsets based on the expression of specific surface molecules and the increase of CD8 effector memory (TEM) cells (identified by the phenotype CD44(+)CD62L(-)) has been shown to mediate protection by releasing of IFN-γ while CD8 central memory (TCM) cells (CD44(+)CD62L(+)) are important for maintaining long-term protection.Identification of multiple CD8 T cell subsets present in the liver relies on the ability to detect multiple surface markers simultaneously.
418 26450377 In this chapter we present a basic 9-color surface staining panel that can be used to identify CD8 TEM, CD8 TCM, short-lived effector cells (SLECs), and memory precursor cells (MPECs) as well as identify those cells which have recently undergone degranulation (surface expression of CD107a).