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Gene Information

Gene symbol: GZMB

Gene name: granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated serine esterase 1)

HGNC ID: 4709

Synonyms: CCPI, CGL-1, CSP-B, CGL1, CTSGL1, HLP, SECT

Related Genes

# Gene Symbol Number of hits
1 AD5 1 hits
2 AFP 1 hits
3 AKT1 1 hits
4 AKT2 1 hits
5 B3GAT1 1 hits
6 BCL2 1 hits
7 BSG 1 hits
8 C9orf140 1 hits
9 CASP1 1 hits
10 CASP3 1 hits
11 CCL2 1 hits
12 CCL3 1 hits
13 CCL4 1 hits
14 CCL5 1 hits
15 CCND3 1 hits
16 CCR5 1 hits
17 CCR7 1 hits
18 CD19 1 hits
19 CD2 1 hits
20 CD27 1 hits
21 CD274 1 hits
22 CD28 1 hits
23 CD34 1 hits
24 CD38 1 hits
25 CD4 1 hits
26 CD40 1 hits
27 CD40LG 1 hits
28 CD44 1 hits
29 CD47 1 hits
30 CD5 1 hits
31 CD69 1 hits
32 CD79A 1 hits
33 CD86 1 hits
34 CD8A 1 hits
35 CD9 1 hits
36 CR2 1 hits
37 CSF2 1 hits
38 CTLA4 1 hits
39 CX3CR1 1 hits
40 CXCL10 1 hits
41 CXCR3 1 hits
42 DNAJC5 1 hits
43 EOMES 1 hits
44 FABP9 1 hits
45 FAS 1 hits
46 FASLG 1 hits
47 FOXP3 1 hits
48 GNLY 1 hits
49 GZMA 1 hits
50 GZMK 1 hits
51 HLA-A 1 hits
52 HLA-B 1 hits
53 HSPA1A 1 hits
54 IFNG 1 hits
55 IL10 1 hits
56 IL12A 1 hits
57 IL15 1 hits
58 IL17A 1 hits
59 IL17C 1 hits
60 IL18 1 hits
61 IL1B 1 hits
62 IL2 1 hits
63 IL4 1 hits
64 IL5 1 hits
65 IL6 1 hits
66 IL7R 1 hits
67 INDO 1 hits
68 ITGAE 1 hits
69 ITGAL 1 hits
70 IV 1 hits
71 JAK3 1 hits
72 KIR3DL1 1 hits
73 KLRD1 1 hits
74 KLRG1 1 hits
75 LAMP1 1 hits
76 LEP 1 hits
77 MAGEA3 1 hits
78 MIRN182 1 hits
79 MLANA 1 hits
80 MME 1 hits
81 NCAM1 1 hits
82 PAGE4 1 hits
83 PAM 1 hits
84 PBRM1 1 hits
85 PDC 1 hits
86 PDCD1 1 hits
87 PRF1 1 hits
88 PROS1 1 hits
89 SERPINB6 1 hits
90 SERPINB9 1 hits
91 SPATA2 1 hits
92 SPN 1 hits
93 STAT3 1 hits
94 TBX21 1 hits
95 TLR3 1 hits
96 TNF 1 hits
97 TNFRSF10A 1 hits
98 TNFRSF8 1 hits
99 TNFSF10 1 hits
100 TP53 1 hits
101 WT1 1 hits
102 XCL1 1 hits
103 ZNF395 1 hits

Related Sentences

# PMID Sentence
1 8995646 For both SIVmac239 and its nef-deleted derivative, strong expression was observed as early as 7 days postinfection for interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha, gamma interferon, and IL-13.
2 8995646 Primary infection with SIVmac239 was characterized by a higher level of IL-4, IL-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES gene expression and a lower level of IL-12 and granzyme B gene expression compared with infection with SIVmac239 delta nef.
3 10068654 Immunization with MPC11 cells expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12) led to long-lasting protection of mice against subcutaneous (sc) challenge with both parental cells or their MDR variants.
4 10068654 Similarly, immunization with GM-CSF/IL-12-transfected MDR sublines caused rejection of transplantation of both parental cells and the MDR sublines.
5 10068654 Whereas MPC11 cells and their MDR variants were resistant to APO-1/CD95/Fas ligand, the immunization generated potent granzyme B/perforin-secreting cytotoxic T lymphocytes (CTLs) that were similarly effective against both parental and isogenic MDR cells.
6 10390075 Upregulation of antitumor immunity by IL-12 gene-transfected AK-5 tumor cells in vivo.
7 10390075 We have earlier demonstrated a significant role for IL-12 in the regression of a rat histiocytic tumor, AK-5.
8 10390075 Analysis of the serum samples from animals injected with the IL-12 gene-transfected AK-5 cells on different days revealed a significant increase in circulatory IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and antitumor antibodies, all of which contributed to the reduction in tumor mass.
9 10390075 Similarly, intraperitoneal transplantation of IL-12 gene-transfected tumor cells in syngeneic Wistar rats induced a significant increase in cellular cytotoxicity, with a concomitant reduction in circulatory IL-12 (p40) protein.
10 10390075 Administration of antibodies to IL-12 and IFN-gamma reduced the expression of the costimulatory molecules B7.1 and B7.2 and the cytolytic effectors granzyme B and Fas-L, suggesting their involvement in IFN-gamma-dependent antitumor immune response induced by IL-12.
11 10687138 The response was mediated by major histocompatibility complex class I-restricted cytotoxic T lymphocytes specific for MART-1 antigen, which produced high levels of interferon-gamma when reexposed to MART-1 in vitro and lysed targets in a calcium-dependent mechanism suggestive of perforin/granzyme B lysis.
12 11714776 A fraction of human CD8+ alphabeta T cells up-regulate 2B4 in vivo, and here we demonstrate that this correlates with the acquisition of effector cell properties such as granzyme B and perforin expression, rapid IFN-gamma production, and down-regulation of the lymph node homing chemokine receptor CCR7.
13 11992409 We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma.
14 11992409 The T-cell population could be further characterized by 4-color flow cytometry in 1 patient, showing that the majority of the peptide-specific CD3(+)CD8(+)IFN-gamma(+) T cells were granzyme B-positive and CCR-7-negative, characterizing them as effector T cells with the ability to mediate cytotoxicity and migrate to inflamed tissues.
15 11992409 A single-site postvaccination relapse occurred in both patients, showing downregulation of tyrosinase expression in 1 patient, while normal expression levels for tyrosinase, MHC class I antigens and components of the antigen-processing machinery were found in the other patient.
16 12065487 Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice.
17 12065487 A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective.
18 12065487 Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes.
19 12065487 Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice.
20 12065487 A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective.
21 12065487 Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes.
22 12065487 Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice.
23 12065487 A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective.
24 12065487 Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes.
25 12200377 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
26 12200377 Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models.
27 12200377 We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients.
28 12200377 T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only.
29 12200377 T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells.
30 12200377 In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+).
31 12200377 These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
32 12601154 To determine whether this difference was due to the low frequency or incomplete maturation of effector CTL in MLN, we measured expression of perforin, granzymes A, B, and C, and IFN-gamma mRNAs in CD8(+) populations and single cells immediately after isolation from virus-infected mice.
33 12601154 Quantitative PCR revealed significant expression of perforin, granzyme A, granzyme B, and IFN-gamma in activated CD8(+) cells from MLN, spleen, and lung parenchyma.
34 12601154 Individual activated or nucleoprotein peptide/class I tetramer-binding CD8(+) cells from the three tissues expressed diverse combinations of perforin, granzyme, and IFN-gamma mRNAs.
35 14729651 Serine protease inhibitor 6 (SPI-6), also called Serpinb9, inhibits granzyme B and thus may provide a method for delaying apoptotic cell death in dendritic cells.
36 14729651 We have previously enhanced DNA vaccine potency by targeting antigen to MHC antigen presentation pathways, using proteins such as Mycobacterium tuberculosis heat shock protein 70, calreticulin, domain II of Pseudomonas aeruginosa exotoxin A, or the sorting signal of the lysosome-associated membrane protein type 1.
37 14729651 This combination of strategies resulted in significantly increased E7-specific CD8+ T-cell and CD4+ Th1-cell responses, enhanced tumor treatment ability, and stronger tumor protection when compared with vaccination without SPI-6.
38 14740954 Little interleukin-4 (IL-4) or IL-10 secretion was detected, indicating a T(H)1 type of T cell response.
39 14740954 T cell depletion studies showed that the interferon-gamma was being secreted by CD4+ T lymphocytes and/or by cells other than CD8+ T lymphocytes that were being stimulated by the CD4+ T lymphocytes.
40 14740954 CD3+ or CD8+ T cell depletion showed that granzyme B mRNA expression correlated with the presence of CD4+ T lymphocytes.
41 14740954 However, depletion of CD4+ T cells after four days of stimulation indicated that the granzyme B mRNA was produced by cells in culture other than lymphocytes.
42 14740954 Little interleukin-4 (IL-4) or IL-10 secretion was detected, indicating a T(H)1 type of T cell response.
43 14740954 T cell depletion studies showed that the interferon-gamma was being secreted by CD4+ T lymphocytes and/or by cells other than CD8+ T lymphocytes that were being stimulated by the CD4+ T lymphocytes.
44 14740954 CD3+ or CD8+ T cell depletion showed that granzyme B mRNA expression correlated with the presence of CD4+ T lymphocytes.
45 14740954 However, depletion of CD4+ T cells after four days of stimulation indicated that the granzyme B mRNA was produced by cells in culture other than lymphocytes.
46 14741160 Serum antibody titers measured by hemagglutination inhibition (HI), and interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and granzyme B (GrzB) levels in ex vivo virus-activated mononuclear cell cultures showed significant responses from pre-vaccination to 4 and 12 weeks post-vaccination (P<0.01).
47 14741160 There was a trend for lower GrzB and higher IFN-gamma and IL-10 levels in healthy versus CHF groups (P<0.06) for all viral strains at 4 weeks.
48 14741160 In the regression model, Grz B levels were significantly predicted by the IFN-gamma:IL-10 ratio and performance on the 6 min Walk Test; age and CHF dropped out of the model.
49 15265915 Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection.
50 15265915 CD4(+)CD28(-) cells had an Ag-primed phenotype and expressed the cytolytic molecules granzyme B and perforin.
51 15265915 CD4(+)CD28(-) cells only produced IFN-gamma after stimulation with CMV-Ag, whereas CD4(+)CD28(+) cells also produced IFN-gamma in response to varicella-zoster virus and purified protein derivative.
52 15265915 Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection.
53 15265915 CD4(+)CD28(-) cells had an Ag-primed phenotype and expressed the cytolytic molecules granzyme B and perforin.
54 15265915 CD4(+)CD28(-) cells only produced IFN-gamma after stimulation with CMV-Ag, whereas CD4(+)CD28(+) cells also produced IFN-gamma in response to varicella-zoster virus and purified protein derivative.
55 15297401 In this pilot study, we show that immunization of three resected, high-risk metastatic melanoma patients with a T-helper epitope derived from the melanoma differentiation antigen, melanoma antigen recognized by T cells-1, results in CD4(+) T-cell immune responses.
56 15297401 Immune reactivity to that epitope was detected by DR4-peptide tetramer staining, and enzyme-linked immunospot assay of fresh and restimulated CD4(+) T cells from patients over the course of the 12-month vaccine regimen.
57 15297401 For 1 DRbeta1*0401(+) patient, antigen-specific CD4(+) T cells recognized human leukocyte antigen-matched antigen-expressing tumor cells, secreted granzyme B, and also exhibited cytolysis that was MHC class II-restricted.
58 15320888 Here, we studied the expression of genes for interferon gamma (IFN-gamma) and molecules involved in lymphocyte-mediated cytotoxicity [granzyme B (grzB), perforin, granulysin and Fas ligand (FasL)] against M. tuberculosis-infected macrophages.
59 15494539 Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine.
60 15494539 Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions.
61 15494539 The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S.
62 15494539 Typhi Ags via HLA-E could stimulate IFN-gamma production.
63 15494539 Typhi GroEL HLA-E binding motifs.
64 15494539 These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.
65 15536147 Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes.
66 15536147 CD40 ligand is an accessory signal for T-cell activation and can overcome T-cell anergy.
67 15536147 Transfer of CD40L and OX40L was observed in all and was followed by the up-regulation of B7-1 and B7-2.
68 15536147 The culture of CD40L/OX40L-expressing B-CLL cells with autologous T cells generated CD4+/CD8+ cytotoxic T-cell lines, which secreted interferon-gamma (IFN-gamma) and granzyme-B/perforin in response to autologous, but not to allogeneic, B-CLL cells or to autologous T-cell blasts.
69 15699131 Exposure to IL-4 during activation of naive murine CD8+ T cells leads to generation of IL-4-producing effector cells with reduced surface CD8, low perforin, granzyme B and granzyme C mRNA, and poor cytolytic function.
70 15699131 CD8 expression positively correlated with perforin and granzyme A, B, and C mRNA, and negatively correlated with IL-4 mRNA levels among these clones.
71 15749916 One month after immunization, vaccinees developed vaccinia virus-specific CD8+ T cells with an effector cell phenotype containing both granzyme A and granzyme B.
72 15749916 One year after immunization, we found a significant decrease in granzyme B containing cells and an increased memory cell phenotype in virus-specific CD8+ T cells.
73 15749916 One month after immunization, vaccinees developed vaccinia virus-specific CD8+ T cells with an effector cell phenotype containing both granzyme A and granzyme B.
74 15749916 One year after immunization, we found a significant decrease in granzyme B containing cells and an increased memory cell phenotype in virus-specific CD8+ T cells.
75 15837235 SD lead to a greater than 10-fold decline in ex vivo interleukin-10 (IL-10) levels (P < .0001) and a corresponding significant increase in the interferon-gamma (IFN-gamma) to IL-10 ratio.
76 15837235 Although BD had no further effect on IL-10 production, the IFN-gamma:IL-10 ratio declined in the BD group (P < .001, A/H3N2 and B strains).
77 15837235 In the SD group only, IFN-gamma:IL-10 ratios significantly correlated with serum antibody titers (R = .37 - .50, P < or = .01) and ex vivo granzyme B (Grz B) levels (R = .50-.65, P < or = .001).
78 15857985 Virus-specific CD4+ and CD8+ cytotoxic T-cell responses and long-term T-cell memory in individuals vaccinated against polio.
79 15857985 The presence of poliovirus (PV)-specific CD4(+) T cells in individuals vaccinated against polio has been shown, but CD8(+) T-cell responses have not been described.
80 15857985 Here, we functionally characterize the CD4(+) T-cell response and show for the first time that dendritic cells and macrophages can stimulate PV-specific CD8(+) T-cell responses in vitro from vaccinees.
81 15857985 Both CD4(+) T and CD8(+) T cells secrete gamma interferon in response to PV antigens and are cytotoxic via the perforin/granzyme B-mediated pathway.
82 15857985 The macrophage-stimulated CD4(+) T and CD8(+) T cells most likely represent memory T cells that persist for long periods in vaccinated individuals.
83 15857985 Thus, immunity to PV vaccination involves not only an effective neutralizing antibody titer but also long-term CD4(+) and CD8(+) cytotoxic T-cell responses.
84 16128921 SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques.
85 16128921 The cDNA for macaque IL-12 and CD40L were cloned into DNA vectors.
86 16128921 Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL-12 or CD40L.
87 16128921 The IL-12 expanded antigen-specific IFN-gamma positive effector cells as well as granzyme B production.
88 16128921 The vaccine immune responses contained both a CD8 component as well a CD4 component.
89 16128921 The adjuvanted DNA vaccines illustrate that IL-12 enhances a CD8 vaccine immune response, however, different cellular profiles.
90 16249392 Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation.
91 16249392 CD40L generates immune responses in leukemia-bearing mice, an effect that is potentiated by IL-2.
92 16249392 We studied the feasibility, safety, and immunologic efficacy of an IL-2- and CD40L-expressing recipient-derived tumor vaccine consisting of leukemic blasts admixed with skin fibroblasts transduced with adenoviral vectors encoding human IL-2 (hIL-2) and hCD40L.
93 16249392 Ten patients (including 7 children) with high-risk acute myeloid (n = 4) or lymphoblastic (n = 6) leukemia in cytologic remission (after allogeneic stem cell transplantation [n = 9] or chemotherapy alone [n = 1]) received up to 6 subcutaneous injections of the IL-2/CD40L vaccine.
94 16249392 These leukemia-reactive T cells included both T-cytotoxic/T-helper 1 (Th1) and Th2 subclasses, as determined from their production of granzyme B, interferon-gamma, and interleukin-5.
95 16339537 IL-2 regulates perforin and granzyme gene expression in CD8+ T cells independently of its effects on survival and proliferation.
96 16339537 We show in this study that IL-2 increased the expression of perforin and granzyme A, B, and C mRNA; intracellular granzyme B protein levels; and cytolytic function in a dose-dependent manner during primary activation of murine CD8+ T cells in vitro.
97 16339537 First, IL-2 enhancement of perforin and granzyme expression was equivalent in CD8+ T cells from wild-type and bcl-2 transgenic mice, although only the latter cells survived in low concentrations or the absence of added IL-2.
98 16339537 This property of bcl-2 transgenic T cells also allowed the demonstration that induction of granzyme A, B, and C mRNA and granzyme B protein required exogenous IL-2, whereas induction of perforin and IFN-gamma expression did not.
99 16339537 Together, these findings indicate that IL-2 can directly regulate perforin and granzyme gene expression in CD8+ T cells independently of its effects on cell survival and proliferation.
100 16339537 IL-2 regulates perforin and granzyme gene expression in CD8+ T cells independently of its effects on survival and proliferation.
101 16339537 We show in this study that IL-2 increased the expression of perforin and granzyme A, B, and C mRNA; intracellular granzyme B protein levels; and cytolytic function in a dose-dependent manner during primary activation of murine CD8+ T cells in vitro.
102 16339537 First, IL-2 enhancement of perforin and granzyme expression was equivalent in CD8+ T cells from wild-type and bcl-2 transgenic mice, although only the latter cells survived in low concentrations or the absence of added IL-2.
103 16339537 This property of bcl-2 transgenic T cells also allowed the demonstration that induction of granzyme A, B, and C mRNA and granzyme B protein required exogenous IL-2, whereas induction of perforin and IFN-gamma expression did not.
104 16339537 Together, these findings indicate that IL-2 can directly regulate perforin and granzyme gene expression in CD8+ T cells independently of its effects on cell survival and proliferation.
105 16424164 Key features of NK cell activity were inhibited, including release of perforin but not granzyme B, as well as the expression of cyclin D3 and activation of the Jak3-mediated pathways.
106 16426858 The frequency of antigen-specific CD4+ and CD8+ T cells can be determined directly in human whole blood by a combination of surface marker and intracellular cytokine staining.
107 16426858 Simultaneously, these lymphocytes can be functionally characterized regarding their differentiation status by analysis of CD45RO and CD27 expression and effector functions by measuring intracellular perforin or granzyme B content.
108 16504351 In contrast, numbers of HLA-A2-pentamer-positive CD8+ T cells and granzyme B-secreting T cells remained unchanged.
109 16504351 Thus, up-regulation of TLR2 during immunization with DC enhances functions of CD4+ T cells but not CD8+ T cells.
110 16622001 In the present study, we used polychromatic flow cytometry to assess the frequency and functional capacity of central memory (CD28(+)CD95(+)) and effector memory (CD28(-)CD95(+)) subpopulations of Gag-specific CD8(+) T cells in SIV/simian human immunodeficiency virus-infected rhesus monkeys.
111 16622001 We observed that vaccination was associated with the preservation of Gag-specific central memory CD8(+) T cells that were functionally capable of producing IFN-gamma, and effector memory CD8(+) T cells that were capable of producing granzyme B following viral Ag exposure.
112 16998881 Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma.
113 16998881 Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients.
114 16998881 Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay.
115 16998881 Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells.
116 16998881 HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls.
117 16998881 Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells.
118 16998881 Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system.
119 17038826 In addition, cellular immune responses, measured as significant increases in CD4+ T-cell proliferation and granzyme B-producing cytotoxic T-cells, were detected against the vaccine strain as well as against heterologous virus strains (H3N2).
120 17081609 Immunization of cattle with a Leptospira borgpetersenii serovar hardjo-bovis vaccine results in the development of a recall response by WC1(+) gammadelta T cells and CD4(+) alphabeta T cells characterized by proliferation and interferon-gamma production.
121 17081609 Both T cell populations had similar transcript profiles for effector molecules, including IFN-gamma, FasL and granzyme B.
122 17081609 In contrast, transcripts for costimulatory receptors and ligands were notably different following activation, as WC1(+) T cells expressed no or lower levels of transcripts for CD28 and CD40L, while CD4(+) T cells expressed substantial levels of both.
123 17081609 These results strengthen the hypothesis that these particular activated WC1(+) and CD4(+) T cells have overlapping effector functions and therefore may differ principally with regard to how they are recruited into immune responses.
124 17082611 Analysis of pretherapy tumors demonstrated that advanced primary tumors were infiltrated by CD4+ and CD8+ T cells with an effector/memory phenotype and CD4+CD25+Foxp3+ T suppressor cells.
125 17082611 Tumor-associated effector memory CD8+ T cells displayed impaired cytotoxic function, whereas CD4+CD25+Foxp3+ cells effectively inhibited T cell proliferation demonstrating functional integrity.
126 17082611 IL-12/GM-CSF treatment promoted a rapid up-regulation of CD43 and CD69 on CD8+ effector/memory T cells, augmented their ability to produce IFN-gamma, and restored granzyme B expression.
127 17082611 Both CD8+ T cell activation and T suppressor cell purge were mediated primarily by IL-12 and required IFN-gamma.
128 17151096 Eight days following infection, we found that 85 to 95% of CD8 T cells exhibit an effector phenotype as indicated by granzyme B, 1B11, CD62L, CD11a, and CD127 expression.
129 17202676 Furthermore, the activated lymphocytes (CD8+) were capable of infiltrating into the tumor site, and much more apoptotic cells along with activation of caspase-3 were observed in the tumors from vaccinated-mice.
130 17202676 Also, high expression levels of human IFN-gamma, TNF-alpha, granzyme B and perforin were detected in the tumors from vaccinated-mice.
131 17237372 Upon isolation from the tumor, the residual tumor-specific T cells were functionally tolerant of tumor Ag as measured by their inability to degranulate and secrete IFN-gamma and granzyme B.
132 17277143 Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8+ T cells with regime-dependent cytokine/granzyme B profiles.
133 17280748 To further evaluate CMI, remaining PBMCs were stimulated overnight with cells infected with each vaccine strain; an increase in spot forming cells (sfc) for Granzyme B and IFN-gamma was found for all subjects and in 51 of 54 sfc tests.
134 17397028 Compared with the native peptide, the agonist (i) bound to HLA-A2 molecules at lower peptide concentrations, (ii) demonstrated a higher stability of the peptide HLA-A2 complex, (iii) induced higher levels of production of IFN-gamma, Granzyme B, TNF-alpha, IL-2 and lymphotactin by PAGE4-specific T-cell lines and (iv) T-cell lines generated against the agonist peptide were more efficient to lyse HLA-A2 human tumor cells expressing native PAGE4.
135 17505023 Induction of a distinct CD8 Tnc17 subset by transforming growth factor-beta and interleukin-6.
136 17505023 Cross-talk between TGF-beta and IL-6 has been shown to direct the differentiation of CD4(+) cells into special IL-17-secreting cells, which are termed Th17 cells.
137 17505023 In this study, we demonstrated that TGF-beta and IL-6 could stimulate CD8(+) cells to differentiate into noncytotoxic, IL-17-producing cells in MLC.
138 17505023 These IL-17-producing CD8(+) cells exhibit a unique granzyme B(-)IFN-gamma(-)IL-10(-) phenotype.
139 17505023 The mRNA level of Th2/T cytotoxic 2 (Tc2) transcription factors GATA3 and Th1/Tc1 transcription factors T-box expressed in T cell (T-bet) as well as its target H2.O-like homeobox (Hlx) is decreased in CD8(+) cells from TGF-beta- and IL-6-treated MLC.
140 17505023 In addition, these CD8(+) cells display a marked up-regulation of retinoic acid-related orphan receptor-gammat, a key IL-17 transcription factor.
141 17505023 These results demonstrate that the existence of an IL-17-producing CD8(+) subset belongs to neither the Tc1 nor the Tc2 subset and can be categorized as a T noncytotoxic 17 (Tnc17) subset.
142 17522859 Specific CD8(+ )T cell responses to HLA-A2 restricted MAGE-A3 p271-279 peptide in hepatocellular carcinoma patients without vaccination.
143 17522859 In this study, we estimated the specific CD8(+) T cell immune response to MAGE-A3 p271-279 peptide (M3(271)) in the peripheral blood of HCC patients without antigen vaccination in order to evaluate its immunotherapeutic potential in these patients.
144 17522859 After expansion in vitro, the functional IFN-gamma producing M3(271) specific CD8(+) T cells were detected in 30.8% (8/26) of HLA-A2(+)MAGE-A3(+) HCC patients.
145 17522859 The effector CD8(+ )T cells could release cytotoxic molecules of granzyme B and perforin after restimulation with natural HLA-A2(+)MAGE-A3(+) HCC cell lines in the samples tested.
146 17522859 The responsive CD8(+ )T cells to both NY-ESO-1 and MAGE-A3 antigens provide a rationale for the application of a bivalent vaccine in HCC patients with tumors expressing both antigens.
147 17570767 A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses.
148 17570767 We constructed a combined DNA vaccine comprising genes encoding the antigens BCSP31, superoxide dismutase (SOD), and L7/L12 and evaluated its immunogenicity and protective efficacy.
149 17570767 Cytokine profiling performed at the same time showed a biased Th1-type immune response with significantly increased interferon-gamma and tumor necrosis factor-alpha stimulation.
150 17570767 CD8(+), but not CD4(+), T cells accumulated at significantly higher levels after administration of the vaccine.
151 17570767 Granzyme B-producing CD8(+) T cells were significantly higher in number in samples prepared from combined DNA-vaccinated mice compared with S19-vaccinated mice, demonstrating that the cytotoxicity lysis pathway is involved in the response to Brucella infection.
152 17823271 HIV-1-specific helper-T-cell activity was studied by measuring the levels of interleukin 2 (IL-2) produced by peripheral blood mononuclear cells (PBMCs) and the granule-dependent CTL activity by measuring the intracellular levels of perforin and granzyme B expression in CD8+ T cells after stimulation with gag p24 antigen.
153 17823271 The levels of perforin and granzyme B expression in CD8+ T cells were also higher among EU individuals than among healthy controls.
154 17823271 HIV-1-specific helper-T-cell activity was studied by measuring the levels of interleukin 2 (IL-2) produced by peripheral blood mononuclear cells (PBMCs) and the granule-dependent CTL activity by measuring the intracellular levels of perforin and granzyme B expression in CD8+ T cells after stimulation with gag p24 antigen.
155 17823271 The levels of perforin and granzyme B expression in CD8+ T cells were also higher among EU individuals than among healthy controls.
156 18158729 Monocyte-derived DCs from healthy donors were infected with the recombinant adenovirus (Ad) harboring HCV NS3 (AdNS3), NS4 (NS4A and NS4B; AdNS4), NS5 (NS5A and NS5B; AdNS5), NS3/NS4 (AdNS3/NS4), and NS4/NS5 (AdNS4/NS5) genes, and then used to stimulate autologous lymphocytes in vitro.
157 18158729 Antigen-specific cellular immune responses were detected by interferon-gamma (IFN-gamma), interleukin 4 (IL-4), and Granzyme B (GrB) enzyme-linked immunospot assays (ELISPOT).
158 18158729 DCs transduced with NS3/NS4 or NS4/NS5 had similar ability to elicit specific immune responses to HCV.
159 18283628 Here we report on the IN VITRO findings of a vaccination trial in five MTC patients, who were treated with a new DC generation protocol consisting of granulocyte-macrophage colony-stimulating factor and interferon-alpha (IFN-DCs).
160 18283628 In two patients who responded to therapy we found a large increase (in mean 2.9+/-1.9%) of antigen-specific IFN-gamma-secreting CD4+ cells as well as an increase of granzyme B positive CD8+ cells (mean 2.2+/-0.2%) in the peripheral blood.
161 18283628 In parallel, a decrease of CD4+/CD25+/FoxP3+ regulatory T cells was seen.
162 18316415 However, only the memory precursors were capable of making interleukin (IL) 2, thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2.
163 18322193 We report that, in sharp contrast to the effector cells (CTLs) that kill DCs in a granzyme B- and perforin-dependent mechanism, memory CD8(+) T cells enhance the ability of DCs to produce IL-12 and to induce functional Th1 and CTL responses in naive CD4(+) and CD8(+) T cell populations.
164 18322193 Moreover, memory CD8(+) T cells that release the DC-activating factor TNF-alpha before the release of cytotoxic granules induce DC expression of an endogenous granzyme B inhibitor PI-9 and protect DCs from CTL killing with similar efficacy as CD4(+) Th cells.
165 18322193 The currently identified DC-protective function of memory CD8(+) T cells helps to explain the phenomenon of CD8(+) T cell memory, reduced dependence of recall responses on CD4(+) T cell help, and the importance of delayed administration of booster doses of vaccines for the optimal outcome of immunization.
166 18322193 We report that, in sharp contrast to the effector cells (CTLs) that kill DCs in a granzyme B- and perforin-dependent mechanism, memory CD8(+) T cells enhance the ability of DCs to produce IL-12 and to induce functional Th1 and CTL responses in naive CD4(+) and CD8(+) T cell populations.
167 18322193 Moreover, memory CD8(+) T cells that release the DC-activating factor TNF-alpha before the release of cytotoxic granules induce DC expression of an endogenous granzyme B inhibitor PI-9 and protect DCs from CTL killing with similar efficacy as CD4(+) Th cells.
168 18322193 The currently identified DC-protective function of memory CD8(+) T cells helps to explain the phenomenon of CD8(+) T cell memory, reduced dependence of recall responses on CD4(+) T cell help, and the importance of delayed administration of booster doses of vaccines for the optimal outcome of immunization.
169 18480841 The induction of antitumor IFN-gamma and granzyme B (GrB)-producing cytotoxic T lymphocytes (CTL) by RNA-transfected DCs was determined by ELISPOT assays.
170 18480841 Both CD3+CD8+ T cells and CD4+CD25+ T cells were expanded without induction of regulatory T cells.
171 18676860 Importantly, they recognized HLA-DRB1*04-matched fresh leukemic cells expressing the WT1 antigen.
172 18676860 These clones exerted a T helper 2 cytokine profile, had a CD4(+)CD25(+)Foxp3(+)GITR(+)CD127(-) T(reg) phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact.
173 18676860 Furthermore, priming of T cells with the WT1-126 HLA-A0201-restricted peptide in the presence of T(regs) strongly inhibited the induction of anti-WT1-126 CD8(+) CTL responses as evidenced by both very low cytotoxic activity and IFN-gamma production.
174 18676860 Moreover, these T(reg) clones specifically produced granzyme B and selectively induced apoptosis in WT1-84-pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells.
175 18676860 Importantly, we have also detected anti-WT1-84 interleukin-5(+)/granzyme B(+)/Foxp3(+) CD4(+) T(regs) in five of eight HLA-DR4(+) acute myeloid leukemia patients.
176 18676860 Importantly, they recognized HLA-DRB1*04-matched fresh leukemic cells expressing the WT1 antigen.
177 18676860 These clones exerted a T helper 2 cytokine profile, had a CD4(+)CD25(+)Foxp3(+)GITR(+)CD127(-) T(reg) phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact.
178 18676860 Furthermore, priming of T cells with the WT1-126 HLA-A0201-restricted peptide in the presence of T(regs) strongly inhibited the induction of anti-WT1-126 CD8(+) CTL responses as evidenced by both very low cytotoxic activity and IFN-gamma production.
179 18676860 Moreover, these T(reg) clones specifically produced granzyme B and selectively induced apoptosis in WT1-84-pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells.
180 18676860 Importantly, we have also detected anti-WT1-84 interleukin-5(+)/granzyme B(+)/Foxp3(+) CD4(+) T(regs) in five of eight HLA-DR4(+) acute myeloid leukemia patients.
181 18820174 Using polychromatic flow cytometry, we simultaneously measured expression of the most common human CEs [granzyme A (gA), granzyme B (gB), and Perf] alongside markers of alphabeta and gammadelta T cell maturation (CD45RO, CCR7, CD27, CD57).
182 18820174 Additionally, we measured CE content in NK cell subsets (defined by their expression of CD16 and CD56).
183 19091870 Higher CS also correlated with higher levels of mRNAs for PD-1, CD4, CD8, F4/80, interleukin-4, gamma interferon, granzyme A, and granzyme B in both cornea and TG.
184 19091870 These results suggest that (i) the immunopathology induced by HSV-1 infection does not correlate with primary virus replication in the eye; (ii) increased CS appears to correlate with increased latency in the TG, although the possible cause-and-effect relationship is not known; and (iii) increased latency in mouse TG correlates with higher levels of PD-1 mRNA, suggesting exhaustion of CD8+ T cells.
185 19109135 Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.
186 19109135 In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression.
187 19109135 TLR2 and TLR5 mRNA was detected in the CD8(+) T cells.
188 19109135 Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5.
189 19109135 The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production.
190 19116651 As soon as 5 days after an intraperitoneal infection with vv, we could identify a subset of CD44(hi) and CD62L(+) vv-specific CD8 T cells in the peritoneal exudate lymphocytes.
191 19116651 This population constituted approximately 10% of all antigen-specific T cells and like central memory T cells, they also expressed high levels of CCR7 and IL-7R but expressed little granzyme B.
192 19155521 Additionally, there was up-regulation of probesets associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities.
193 19155521 The strongest correlations with neutralizing Ab titers were found for cyclin D2 (CCND2) and galectin (LGALS2).
194 19248785 Addition of different amounts of peptide (10-80 microg) to a mixed lymphocyte peptide culture (MLPC) resulted in the generation of interferon (IFN) gamma and granzyme B releasing CD8(+) CMV tetramer(+) T cells in a dose dependent manner.
195 19483645 T-cells cocultured with these DC showed decreased expression of interferon-gamma and granzyme B, and lowered proliferation when compared with T-cells cocultured with DC generated from frozen monocytes or DC generated from freshly isolated monocytes.
196 19733584 The experimental data demonstrated that this SL(E6-85B) vaccine, or when it is combined with BCG vaccination, induced the strongest TB Ag-specific mucosal, humoral, and cellular immune responses comprised of increased proliferation of T cells, IFN-gamma expression, granzyme B production, as well as the greatest IFN-gamma production of effector-memory T (T(EM)) or effector CD8(+) T cell responses and exerted high protective efficacy in mice against virulent M. tb H37Rv challenge compared to the other vaccinated groups (mice immunized with SL(Ag85B), a DNA vaccine or BCG only).
197 19747576 Moreover even when variants were recognized, the IFN-gamma and granzyme B responses as well as T-cell proliferation were of lower magnitude.
198 19803378 'Help' from CD4+ T cells is important for the differentiation of naive CD8+ T cells to effector and memory CD8+ cytotoxic T cells.
199 19803378 To elucidate the role of Th polarization on the 'Help' function of CD4+ T cells, we established an in vitro culture system using OVA specific CD8+ T cells, Peptide-25 specific CD4+ T cells and splenic dendritic cells (DCs).
200 19803378 The DCs that were pre-cultured with Peptide-25 specific CD4+ T cells together with OVA and Peptide-25 induced the proliferation and granzyme B production of OVA specific CD8+ T cells.
201 19803378 On the other hand, the DCs that were pre-cultured with Peptide-25 specific CD4+ T cells together with OVA and APL induced only proliferation of OVA specific CD8+ T cells.
202 19923181 The majority of vaccine-specific CD4(+) and CD8(+) T cells lacked gamma interferon production but showed high antigen-specific proliferation capacities.
203 19923181 Proliferative CD8(+) T cells expressed the lytic molecule granzyme B.
204 20018619 In this study, we report that although Ags presented by different types of mature dendritic cells (DCs) are similarly effective in inducing CD8+ T cell expansion, the acquisition of CTL function and peripheral-type chemokine receptors, CCR5 and CXCR3, requires Ag presentation by a select type of DCs.
205 20018619 However, granzyme B expression, acquisition of CTL activity, and peripheral tissue-type chemokine responsiveness are features exclusively exhibited by CD8+ T cells activated by DC1s.
206 20097089 LIGHT could potentiate the proliferation of T lymphocytes and induction of T CD8(+) cells performing by measuring Granzyme B, a specific marker of CMI immunity and virus neutralization antibody titer.
207 20101613 These protective CD8(+) T cells from immune WT mice had the potential to generate IFN-gamma, perforin (PFN) and granzyme B.
208 20101613 When mice deficient in IFN-gamma were used as donor mice for CD8(+) T cells, protective immunity in the host mice was fully abrogated, and the immunity was profoundly attenuated in PFN-deficient mice.
209 20101613 Thus, CD8(+) T cells producing IFN-gamma and PFN appear to be involved in protective immunity against infection with blood-stage malaria.
210 20121402 In comparison to concordant patients, discordant patients showed poor lymphocyte proliferation, lower secretion of IL-2 and IFN-gamma, a lower percentage of perforin and granzyme-B-producing CD8 T cells, and poor differentiation of effector memory CD8 T(EM) cells into CD8 T(EMRA) cells in in-vitro stimulation assays, especially against HIV-1 Gag p24 and one of its peptide pools.
211 20121402 Our results suggest that prolonged suppression of plasma viremia alone does not warrant good qualitative and quantitative CD8 T-cell responses to HIV-1, implying that CD4 T cells are required for maintenance of protective CD8 T-cell responses.
212 20174562 Tetramer analysis further showed that up to 16.8% of all circulating CD3(+)CD8(+) T cells were specific for the single HLA-B*3501-restricted epitope Gn(465-473) years after the acute infection.
213 20174562 Remarkably, Gn(465-473)-specific cells readily secreted IFN-gamma, granzyme B and TNF-alpha but not IL-2 upon stimulation and showed a 'revertant' CD45RA(+)CD27(-)CD28(-)CCR7(-)CD127(-) effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections.
214 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.
215 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.
216 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.
217 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.
218 20635955 We observed a higher than expected loss of activity from the injection point (median A(t)/A(0) = 0.60 at day 2), which correlated with an increase in total cytotoxic T lymphocytes (CD8(+) and granzyme B(+) cells) in the lypmphoid tissue observed after immunization (R(2) = 0.92, p = 0.03).
219 20646987 In LCI subjects who did not seroconvert to influenza infection, pre-infection levels of the cytolytic mediator, granzyme B, correlated with fever (r=1.000; p=0.01) and the IFN-gamma:IL-10 ratio (r=0.999; p=0.03), and increased following influenza infection in LCI vs.
220 20795543 Differential regulation of the cytotoxic proteins, granzyme A, granzyme B and perforin are also observed in virus-specific T cells following infection.
221 21039472 Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii.
222 21039472 It is widely accepted that antibodies and CD4 T cells play critical roles in the immune response during the blood stage of malaria, whereas the role of CD8 T cells remains controversial.
223 21039472 Here, we show that both CD8 and CD4 T cells robustly responded to an acute self-limiting blood-stage infection with Plasmodium yoelii.
224 21039472 Similar to antigen-specific T cells, both CD8 and CD4 T cells showed dynamic expression of the surface proteins interleukin (IL)-7R and programmed death-1 (PD-1).
225 21039472 Additionally, activated CD8 T cells showed differences in the expression of Killer cell lectin-like receptor G1, L-selectin and B cell lymphoma-2 and produced granzyme B, indicating cytotoxic activity, and the initially high expression of T-box transcription factor TBX21 in malaria-activated CD4 T cells indicated an early T helper type 1 (Th1)-skewed immune response.
226 21039472 Our data demonstrate that blood-stage malaria infection results in a striking T-cell response and that activated CD8 and CD4 T cells have phenotypic and functional characteristics that are consistent with conventional antigen-specific effector and memory T cells.
227 21039472 Therefore, a better understanding of the CD8 and CD4 T-cell response induced by blood-stage infection may prove to be essential in the development of a vaccine that targets the erythrocytic stage of the malarial parasite.
228 21041491 These were pulsed with heat-killed B. pseudomallei or purified antigens, including ABC transporters (LolC, OppA, and PotF), Bsa type III secreted proteins (BipD and BopE), tandem repeat sequence-containing proteins (Rp1 and Rp2), flagellin, and heat shock proteins (Hsp60 and Hsp70), prior to being mixed with autologous T-cell populations.
229 21041491 After pulsing of cells with either heat-killed B. pseudomallei, LolC, or Rp2, coculturing the antigen-pulsed moDCs with T cells elicited gamma interferon production from CD4(+) T cells from seropositive donors at levels greater than those for seronegative donors.
230 21041491 These antigens also induced granzyme B (cytotoxic) responses from CD8(+) T cells.
231 21148794 Loss of IL-17-producing CD8 T cells during late chronic stage of pathogenic simian immunodeficiency virus infection.
232 21148794 Although IL-17-secreting CD4 (Th17) and CD8 (Tc17) T cells have been reported, very little is known about the latter subset for any infectious disease.
233 21148794 Notably, ∼50% of Tc17 cells also expressed the co-inhibitory molecule CTLA-4, and only a minority (<20%) expressed granzyme B suggesting that these cells possess more of a regulatory than cytotoxic phenotype.
234 21239717 Pretreatment of naive B cells with CpG ODN also enabled presentation of tetanus toxoid to CD8(+) T cells, resulting in CD8(+) T cell cytokine production and granzyme B secretion and proliferation.
235 21277409 Gp96 SIV Ig immunization induces potent polyepitope specific, multifunctional memory responses in rectal and vaginal mucosa.
236 21277409 Tetramer positive CD8 CTL expressed appropriate functional (granzyme B) and migration markers (CD103).
237 21277409 The polyepitope specificity of the mucosal CD8 and CD4 response is evident from a strong, multifunctional cytokine response upon stimulation with peptides covering the gag, tat and env proteins.
238 21383976 Increased cytotoxic capacity of HIV-specific CD8+ T-cells associated with efficient elimination of HIV-infected CD4+ T-cell targets has been shown to distinguish long-term nonprogressors (LTNP), patients with durable control over HIV replication, from those experiencing progressive disease.
239 21383976 Here, measurements of granzyme B target cell activity and HIV-1-infected CD4+ T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5) HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP.
240 21383976 Although the recall cytotoxic capacity of the CD8+ T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection.
241 21383976 These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8+ T-cell cytotoxic responses.
242 21491085 In this study, we created a lentivirus expressing the AFP antigen and investigated the anti-tumor activity of AFP-specific CD8+ T cells, with and without CD4+ T cells, which were activated by either AFP peptide-pulsed or Lenti-AFP-engineered Dendritic cells (DCs) in vitro and in vivo.
243 21491085 AFP-specific T cells could efficiently kill HepG2 HCC cells, and produced IL-2, IFN-γ, TNF-α, perforin and granzyme B, with minimal production of IL-10 (a negative regulator of T cell activation).
244 21518876 The IL-6 acted by inducing granzyme B production and reducing expression of inhibitory molecule PD1 on the surface of the primed CD8 T cells.
245 21527558 In vaccinated mice, silencing STAT3 increased the proliferation and granzyme B levels of intratumoral CD4(+) and CD8(+) T cells.
246 21765403 Although the majority of HIV-specific CD8(+) T cells lose proliferative capacity during chronic infection, T cells restricted by HLA-B*27 or HLA-B*57 allele groups do not.
247 21765403 This differential sensitivity of HIV-specific CD8(+) T cells to T(reg) cell-mediated suppression correlates with their expression of the inhibitory receptor T cell immunoglobulin domain and mucin domain 3 (Tim-3) after stimulation with their cognate epitopes.
248 21765403 Furthermore, we show that HLA-B*27- and HLA-B*57-restricted effectors also evade T(reg) cell-mediated suppression by directly killing T(reg) cells they encounter in a granzyme B (GzmB)-dependent manner.
249 21843950 IL-1 strikingly enhances antigen-driven responses of CD4 and CD8 T cells.
250 21843950 The effect is mediated by direct action on CD4 and CD8 T cells; the response occurs when OT-I or OT-II cells are transferred to B6 IL-1R1-/- recipients and only cells that express IL-1 receptors can respond.
251 21843950 IL-1 enhances the proportion of responding CD4 T cells that differentiate into Th17 cells and increases the proportion of responding CD8 cells that express granzyme B.
252 21849445 This attenuation correlates with more effective immune responses in the absence of SPI-2, including an earlier serum gamma interferon (IFN-γ) response, raised serum interleukin 18 (IL-18), increased numbers of granzyme B(+) CD8(+) T cells, and, most notably, increased numbers and activation of NK cells.
253 21853094 Elimination of adoptively transferred MHC-I(neg) splenocytes was unimpaired in the absence of gzmA and gzmB, but dependent on perforin.
254 22039016 IL-17/IFN-γ double producing CD8+ T (Tc17/IFN-γ) cells: a novel cytotoxic T-cell subset converted from Tc17 cells by IL-12.
255 22039016 It has been reported that IFN-γ-producing CD8(+) T (Tc1) cells express cytotoxic molecules such as perforin and granzyme B to exhibit higher cytotoxicity against tumor cells compared with Tc2 cells.
256 22039016 However, the critical role of IL-17-producing CD8(+) T (Tc17)-cell subsets in tumor immunity remains unclear.
257 22294447 Two weeks after three subcutaneous doses of DNA vaccine, the mice were challenged intranasally with 1 LD50 of A/Puerto Rico/8/34 (H1N1) virus, and PB1- and HA-specific antibodies, survival rate, body weight change, viral mRNA load, infectious virus titer in the lungs, cytokines IL-2, IL-4 and IL-10, and granzyme-B were measured.
258 22532670 Using polychromatic flow cytometry, we measured levels of degranulation, cytokine expression (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]), and the cytolytic mediator granzyme B.
259 22532670 In vivo killing assays revealed that CD8(+) T cells specific for both viruses were equally cytolytic (∼80% target cell lysis after 4 h), consistent with the similar levels of granzyme B and degranulation detected among these cells.
260 22532670 Using polychromatic flow cytometry, we measured levels of degranulation, cytokine expression (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]), and the cytolytic mediator granzyme B.
261 22532670 In vivo killing assays revealed that CD8(+) T cells specific for both viruses were equally cytolytic (∼80% target cell lysis after 4 h), consistent with the similar levels of granzyme B and degranulation detected among these cells.
262 22674985 Normal human peripheral blood mononuclear cells were used to derive HIV-infected CD4(+) T cell targets and autologous, freshly isolated, natural killer (NK) cells in a novel assay that measures granzyme B (GrB) and HIV-1-infected CD4(+) T cell elimination (ICE) by flow cytometry.
263 22674985 We observed that complex sera mediated greater levels of ADCC than anti-HIV-1 envelope glycoprotein (Env)-specific monoclonal antibodies and serum-mediated ADCC correlated with the amount of IgG and IgG1 bound to HIV-1-infected CD4(+) T cells.
264 22720235 While T cells loaded with a class I-restricted peptide induced proliferation but not effector differentiation of antigen-specific CD8 T cells, injection of T cells co-pulsed with αGC strongly induced IFNγ and Granzyme B expression in T cells and complete lysis of target cells in vivo.
265 22720235 Of note, the generation of this cytotoxic T cell response was independent of IL-4, IFNγ, IL-12, IL-21 and costimulation.
266 22735807 We have previously shown that vaccination with the natural tumor peptide Melan-A-induced T cells with superior effector functions as compared with vaccination with the analog peptide optimized for enhanced HLA-A*0201 binding.
267 22735807 Here we found that natural peptide vaccination induced tumor-reactive CD8 T cells with frequent coexpression of both memory/homing-associated genes (CD27, IL7R, EOMES, CXCR3, and CCR5) and effector-related genes (IFNG, KLRD1, PRF1, and GZMB), comparable with protective Epstein-Barr virus-specific and cytomegalovirus-specific T cells.
268 22802414 Antiangiogenic tumor therapy by DNA vaccine inducing aquaporin-1-specific CTL based on ubiquitin-proteasome system in mice.
269 22802414 Given that in APC ubiquitinated peptides are effectively introduced into proteasomes from which CD8 epitopes are excised, we fused ubiquitin with AQP-1 (pUB-AQP-1) to produce a DNA vaccine.
270 22802414 The antitumor effect of the pUB-AQP-1 DNA vaccine was largely mediated by CD8 T cells, which secrete IFN-γ, perforin, and granzyme-B in the presence of APCs transfected with pUB-AQP-1.
271 22942184 T-box transcription factors T-bet (Tbx21) and Eomesodermin (Eomes) are critical players in CD8(+) cytotoxic T lymphocyte effector function and differentiation, but how the expression of these transcription factors is regulated remains poorly defined.
272 22942184 Here we show that dominant T cells directed toward human CMV, expressing significantly higher levels of T-bet with graded loss of Eomes expression (T-bet(hi)Eomes(hi/lo)), are more efficient in recognizing endogenously processed peptide-major histocompatibility complexes (pMHC) compared with subdominant virus-specific T cells expressing lower levels of T-bet and high levels of Eomes (T-bet(int)Eomes(hi)).
273 22942184 Paradoxically, the T-bet(hi)Eomes(hi/lo) dominant populations that efficiently recognized endogenous antigen demonstrated lower intrinsic avidity for pMHC, whereas T-bet(int)Eomes(hi) subdominant populations were characterized by higher pMHC avidity and less efficient recognition of virus-infected cells.
274 22942184 Importantly, differential endogenous viral antigen recognition by CMV-specific CD8(+) T cells also correlated with the differentiation status and expression of perforin, granzyme B and K.
275 22942184 Furthermore, we demonstrate that the expression of T-bet correlates with clonal expansion, differentiation status, and expression of perforin, granzyme B and K in antigen-specific T cells.
276 22942184 T-box transcription factors T-bet (Tbx21) and Eomesodermin (Eomes) are critical players in CD8(+) cytotoxic T lymphocyte effector function and differentiation, but how the expression of these transcription factors is regulated remains poorly defined.
277 22942184 Here we show that dominant T cells directed toward human CMV, expressing significantly higher levels of T-bet with graded loss of Eomes expression (T-bet(hi)Eomes(hi/lo)), are more efficient in recognizing endogenously processed peptide-major histocompatibility complexes (pMHC) compared with subdominant virus-specific T cells expressing lower levels of T-bet and high levels of Eomes (T-bet(int)Eomes(hi)).
278 22942184 Paradoxically, the T-bet(hi)Eomes(hi/lo) dominant populations that efficiently recognized endogenous antigen demonstrated lower intrinsic avidity for pMHC, whereas T-bet(int)Eomes(hi) subdominant populations were characterized by higher pMHC avidity and less efficient recognition of virus-infected cells.
279 22942184 Importantly, differential endogenous viral antigen recognition by CMV-specific CD8(+) T cells also correlated with the differentiation status and expression of perforin, granzyme B and K.
280 22942184 Furthermore, we demonstrate that the expression of T-bet correlates with clonal expansion, differentiation status, and expression of perforin, granzyme B and K in antigen-specific T cells.
281 22966165 We observed that FSME-activated pDCs specifically lysed NK target cells and expressed cytotoxic molecules, such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and granzyme B.
282 23015705 Activating KIR copy number variation is associated with granzyme B release by NK cells during primary simian immunodeficiency virus infection in rhesus monkeys.
283 23015705 Here we show that the number of activating killer cell immunoglobulin-like receptor (KIR) copies in rhesus monkeys is associated with the extent of release of cytotoxic granules by cytolytic NK cells during primary simian immunodeficiency virus SIVmac251 infection.
284 23052295 Flow cytometric analysis revealed the induction of HPV-specific CD8(+) T cells that efficiently loaded granzyme B and perforin and exhibited full cytolytic functionality in all cohorts.
285 23144947 CXCL10 is critical for the generation of protective CD8 T cell response induced by antigen pulsed CpG-ODN activated dendritic cells.
286 23144947 Moreover, we demonstrate that the induction of protective immunity conferred by SLA-CpG-DCs depends entirely on the CXC chemokine IFN-γ-inducible protein 10 (CXCL10; IP-10).
287 23144947 CXCL10 also contributed towards the generation of perforin and granzyme B, two important cytolytic mediators of CD8⁺ T cells, following SLA-CpG-DCs vaccination.
288 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.
289 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).
290 23284789 Interleukin-15-induced CD56(+) myeloid dendritic cells combine potent tumor antigen presentation with direct tumoricidal potential.
291 23284789 Notwithstanding marked expression of the natural killer (NK) cell marker CD56 on a subset of IL-15 DCs, we found no evidence of a further phenotypic overlap between IL-15 DCs and NK cells.
292 23284789 The cytotoxicity of IL-15 DCs is predominantly mediated by granzyme B and, to a small extent, by tumor necrosis factor-α (TNF-α)-related apoptosis-inducing ligand (TRAIL) but is independent of perforin, Fas ligand and TNF-α.
293 23338237 We observed the loss of the short-lived effector cell phenotype (reduced KLRG1(+), T-bet(hi), granzyme B(hi)), accompanied by an enhanced memory precursor phenotype at the effector (increased CD127(hi), IL-2(+)) and contraction phases (increased CD127(hi), IL-2(+), eomesodermin(hi)) of the CD8 response in the absence of RA signaling.
294 23357382 CD8 T cells also upregulate CD11a, CD11b, and CD11c upon activation.
295 23357382 To determine the function of individual β2 integrins, we examined CD8 T cell responses to Listeria monocytogenes infection in CD11a-, CD11b-, and CD11c-deficient mice.
296 23357382 The absence of CD11b or CD11c had no effect on the generation of antigen-specific CD8 T cells.
297 23357382 Moreover, the response in CD11a(-/-) mice exhibited reduced differentiation of short-lived effector cells (KLRG1(hi) CD127(lo)), although cytokine and granzyme B production levels were unaffected.
298 23408627 A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease.
299 23408627 All four immunizations generated mucosal SIV-specific IgA.
300 23408627 Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes.
301 23408627 Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples.
302 23408627 Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization.
303 23408627 The majority of SIV-specific T cells that produced granzyme B did not produce cytokines.
304 23408627 A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease.
305 23408627 All four immunizations generated mucosal SIV-specific IgA.
306 23408627 Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes.
307 23408627 Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples.
308 23408627 Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization.
309 23408627 The majority of SIV-specific T cells that produced granzyme B did not produce cytokines.
310 23468632 SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4(+) T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4(+) T-cell elimination (ICE).
311 23468632 In addition, significant correlations between ICE and viral load (r = -0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, p<0.001) were observed.
312 23468632 These findings support that greater lytic granule loading of virus-specific CD8(+) T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans.
313 23468632 SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4(+) T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4(+) T-cell elimination (ICE).
314 23468632 In addition, significant correlations between ICE and viral load (r = -0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, p<0.001) were observed.
315 23468632 These findings support that greater lytic granule loading of virus-specific CD8(+) T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans.
316 23478322 Granule exocytosis of granulysin and granzyme B as a potential key mechanism in vaccine-induced immunity in cattle against the nematode Ostertagia ostertagi.
317 23478322 A correlation study between the parasitological parameters and gene transcription levels showed that the transcription levels of two of the upregulated genes, those for granulysin (GNLY) and granzyme B (GZMB), were negatively correlated with cumulative fecal egg counts and total worm counts, respectively.
318 23478322 Both genes were also positively correlated with each other and with another upregulated gene, that for the IgE receptor subunit (FCER1A).
319 23478322 Granule exocytosis of granulysin and granzyme B as a potential key mechanism in vaccine-induced immunity in cattle against the nematode Ostertagia ostertagi.
320 23478322 A correlation study between the parasitological parameters and gene transcription levels showed that the transcription levels of two of the upregulated genes, those for granulysin (GNLY) and granzyme B (GZMB), were negatively correlated with cumulative fecal egg counts and total worm counts, respectively.
321 23478322 Both genes were also positively correlated with each other and with another upregulated gene, that for the IgE receptor subunit (FCER1A).
322 23589106 The proportion of granzyme B-positive CD8(+) T cells was increased only in patients from arm C but not in arm B.
323 23811319 Depletion of regulatory T cells by targeting folate receptor 4 enhances the potency of a GM-CSF-secreting tumor cell immunotherapy.
324 23811319 Combination therapy increased expression of IFN-γ and granzyme B by CD8 T cells.
325 23824804 All five individual peptides and epitopes of peptide-pool F3 induced IFN-γ and/or proliferation responses in addition to inducing CTL-associated cytotoxin responses (perforin, granzyme A, granzyme B).
326 23894722 TLR3 agonists improve the immunostimulatory potential of cetuximab against EGFR+ head and neck cancer cells.
327 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.
328 23894722 The DC-mediated cross priming of EGFR-specific CD8+ T cells was monitored upon in vitro stimulation with tetramer-based flow cytometry.
329 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.
330 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.
331 23894722 Furthermore, DCs matured in these conditions exhibited improved cross-priming abilities, resulting in higher numbers of EGFR-specific CD8+ T cells.
332 23897618 Sustained production of IFN-γ, interleukin-2, and tumor necrosis factor alpha was elicited in both the CD4(+) and CD8(+) T cell compartments.
333 23897618 Notably, antigen-specific CD8(+) granzyme B(+) T cells were observed in NHPs.
334 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).
335 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).
336 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).
337 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).
338 23949283 Improved cytotoxic T-lymphocyte immune responses to a tumor antigen by vaccines co-expressing the SLAM-associated adaptor EAT-2.
339 23949283 Also, an increase in MC-38 tumor cell apoptosis (as measured by hematoxylin and eosin staining, active caspase-3 and granzyme B levels within the tumors) was observed.
340 23956116 Minor histocompatibility antigen HA-1-specific cytotoxic lymphocyte (CTL) clones have apparent anti-leukaemic efficacy, and the AML/ETO gene is a special fusion gene in leukaemic cells.
341 23956116 Thus, we hypothesised that a vaccine targeting HA-1 and AML/ETO could stimulate NK cells to target leukaemia cells.
342 23956116 The level of miR-182, which targets ULBP2, significantly decreased with increasing IFN-γ and granzyme B in a co-recombinant group.
343 23956116 In summary, DNA vaccines including AML/ETO and HA-1 fragments significantly enhance the innate immunity of NK cells in vitro.
344 24051432 A DNA vaccine targeting p42.3 induces protective antitumor immunity via eliciting cytotoxic CD8+T lymphocytes in a murine melanoma model.
345 24051432 Immunized mice showed a high level of specific cytotoxic activity against the p42.3 protein in vivo and had activated CD8 T cells that secreted IFN-γ, perforin, and granzyme B in response to stimulation with the antigen in vitro.
346 24067957 The programmed death receptor 1 ligand/programmed death receptor 1 (PDL-1/PD-1) pathway plays an important immunoregulatory role, particularly in the context of T cell function.
347 24067957 Using in vitro cocultures of airway epithelial cells and T cells and in vivo models of influenza virus infection, we have demonstrated that blockade of airway epithelial PDL-1 improves CD8 T cell function, defined by increased production of gamma interferon (IFN-γ) and granzyme B and expression of CD107ab.
348 24067957 Our findings suggest that local manipulation of the PDL-1/PD-1 axis in the airways may represent a therapeutic alternative during acute influenza virus infection.
349 24083086 Importantly, VSV-boosted CD8+ T cells were more potent than those primed by adenoviruses only, as measured by cytokine production, granzyme B expression, and functional avidity.
350 24092469 Immunization in the presence of IL-1β increases the frequency of IL-17- and IFN-γ-producing cells among primed CD4 cells and the frequency of granzyme B-expressing and IFN-γ-producing cells and of cytotoxic cells among primed CD8 cells.
351 24360890 We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses.
352 24360890 We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05).
353 24360890 We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05).
354 24497611 Recently, we reported that the combination of CpG and IL-21 (CpG/IL-21) can induce granzyme B (GrB)-dependent apoptosis in B-CLL cells.
355 24497611 APC- and CTL-typical molecules found to be up-regulated in CpG/IL-21-stimulated B-CLL cells include GrB, perforin, T-bet, monokine-induced by IFN-γ and IFN-γ-inducible protein 10 (IP-10), as well as molecules important for cell adhesion, antigen cross-presentation and costimulation.
356 24497611 Also induced are molecules involved in GrB induction, trafficking and processing, whereas the GrB inhibitor Serpin B9 [formerly proteinase inhibitor-9 (PI-9)] is down-modulated by CpG/IL-21.
357 24631092 Our results show that an optimum dose of adenovirus vector (2×10(7)pfu/mouse) administered intramuscularly (i.m.) induces high T cell proliferation, granzyme B-expressing CD8(+) T cells, pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-2 and IL-6, and antibody responses that can significantly reduce the Vac-HCV viral load in the ovaries of female C57BL/6 mice.
358 24782871 CD4(+) T cells contribute to tumor eradication, even in the absence of CD8(+) T cells.
359 24782871 In a TCR-transgenic B16 melanoma model, MHCII(POS) melanoma cells are directly killed by cytotoxic CD4(+) T cells in a perforin/granzyme B-dependent manner.
360 24786587 Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more.
361 24786587 A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ.
362 24786587 We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection.
363 24786587 Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more.
364 24786587 A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ.
365 24786587 We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection.
366 24894091 Immunohistochemical data of infiltrating (suppressive) cells, such as T cells, regulatory T cells, myeloid-derived suppressor cells, and mast cells, or the expression of T-cell inhibitory factors (PD-1/PD-L1, IDO, and galectins), cytotoxic molecules (granzyme-B), melanocyte differentiation antigens, HLA class-I and tolerogenic cytokines [interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-β] were correlated statistically to clinical outcome and overall survival (OS).
367 24894091 Significantly more tumor-infiltrating CD4(+) and CD8(+) T cells (both P < 0.05) were found in nonprogressors to vaccination (n = 9; median OS, 56 months), compared with progressors (n = 18; median OS, 9.5 months).
368 24894091 Our study shows that high numbers of intratumoral activated CD4(+) or CD8(+) T cells, before autologous tumor cell vaccination, are associated with favorable clinical outcome.
369 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.
370 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.
371 24999042 HIV replication in conjunction with granzyme B production by CCR5+ memory CD4 T cells: Implications for bystander cell and tissue pathologies.
372 24999042 Both GrzB and HIV expression were mainly restricted to CCR5-expressing memory CD4+CD45RO+ T cells, including Th1 and Th17 subsets.
373 24999042 These results suggest that GrzB from CCR5+ memory CD4 T cells may have a role in cellular and tissue pathologies during HIV infection.
374 25043277 Based on our results, we suggest four correlates of cellular protection for the assessment of protective rickettsial antigens: (1) production of IFN-γ by antigen-experienced CD3(+)CD8(+)CD44(high) cells, (2) production of Granzyme B by CD27(low)CD43(low) antigen-experienced CD8(+) T cells, (3) generation of memory-type CD8(+) T cells [Memory Precursor Effector Cells (MPECs), as well as CD127(high)CD43(low), and CD27(high)CD43(low) CD8(+) T cells], and (4) generation of effector-like memory CD8(+) T cells (CD27(low)CD43(low)).
375 25083327 Radiotherapy and Lm vaccine each induce different aspects of antitumor immunity, resulting in an overall increase in intratumoral numbers of activated T cells, antigen-specific CD8+ T cells, natural killer (NK) cells and levels of effector molecules, such as interferon γ (IFNγ) and granzyme B.
376 25246494 The inhibitory receptor programmed death-1 (PD-1) has been shown to regulate CD8 T cell function during chronic SIV infection; however, its role on CD4 T cells, specifically in the gut-associated lymphoid tissue, is less well understood.
377 25246494 In this study, we show that a subset of CD4 T cells expresses high levels of PD-1 (PD-1(hi)) in the rectal mucosa, a preferential site of virus replication.
378 25246494 The majority of these PD-1(hi) CD4 T cells expressed Bcl-6 and CXCR5, markers characteristic of T follicular helper cells in the lymph nodes.
379 25246494 Following a pathogenic SIV infection, the frequency of PD-1(hi) cells (as a percentage of CD4 T cells) dramatically increased in the rectal mucosa; however, a significant fraction of them did not express CXCR5.
380 25246494 Interestingly, vaccinated SIV controllers did not present with this aberrant PD-1(hi) CD4 T cell enrichment, and this lack of enrichment was associated with the presence of higher frequencies of SIV-specific granzyme B(+) CD8 T cells within the lymphoid tissue, suggesting a role for antiviral CD8 T cells in limiting aberrant expansion of PD-1(hi) CD4 T cells.
381 25246494 These results highlight the importance of developing vaccines that enhance antiviral CD8 T cells at sites of preferential viral replication and support the need for developing therapeutic interventions that limit expansion of SIV(+)PD-1(hi) CD4 T cells at mucosal sites as a means to enhance viral control.
382 25297630 Here, we report that CD47 blockade directly enhances tumor immunosurveillance by CD8(+) T cells.
383 25297630 Combining CD47 blockade with irradiation did not affect fibrosarcoma growth in T cell-deficient mice, whereas adoptive transfer of tumor-specific CD8(+) T cells restored combinatorial efficacy.
384 25297630 CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8(+) CTL-mediated tumor cell killing in vitro.
385 25297630 Mechanistic investigations revealed increased tumor infiltration by cytotoxic CD8(+) T cells in a CD47-deficient microenvironment, with an associated increase in T cell-dependent intratumoral expression of granzyme B.
386 25297630 Correspondingly, an inverse correlation between CD8(+) T-cell infiltration and CD47 expression was observed in human melanomas.
387 25297630 Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8(+) cytotoxic T cells, with the potential to increase curative responses.
388 25382510 The neoplastic cells reacted positively for CD56, CD3, CD2, perforin, and granzyme B, but negatively for CD4, CD8, CD10, CD19, CD30, CD34, CD79, and betaF1.
389 25395301 Here, we test the impact of antigen persistence on mouse CD8 and CD4 T cell distribution and differentiation by comparing responses to infections with different strains of LCMV that cause either acute or chronic infections.
390 25395301 Persistent infection also maintained mucosal-homing α4β7 integrin expression, higher granzyme B expression, alterations in the expression of the TRM markers CD69 and CD103, and greater accumulation of virus-specific CD8 T cells in the large intestine, liver, kidney, and female reproductive tract.
391 25395301 This study clarifies the relationship between viral persistence and CD4 and CD8 T cell distribution and mucosal phenotype, indicating that chronic LCMV infection magnifies T cell migration to nonlymphoid tissues.
392 25466267 In vitro, the MP-based vaccine significantly increased dendritic cell (DC) activation with up-regulated CD40 and CD80 expression and IL-12 production compared to alum-based vaccine.
393 25466267 Moreover, subcutaneous and intramuscular immunizations with MP-based vaccine augmented Granzyme B, Th1-type cytokines (IL-2, IL-12, and IFN-γ), and Th2 cytokine IL-4 secretions.
394 25483651 MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration.
395 25483651 In this study, we have identified 9 short peptides derived from MAGED4B protein that are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24).
396 25483651 The peptides had good binding affinity with the MHC-Class I molecules and stimulated ex-vivo IFN-gamma and Granzyme-B production in blood samples from OSCC patients, suggesting that they are immunogenic.
397 25559187 DNA vaccination with SIV Gag induced antigen-specific CD4(+) and CD8(+) T cells in the absence of IL-15.
398 25559187 Importantly, boosting by DNA 8-months after vaccination revealed severely reduced granzyme B content in CD8(+) T cells of IL-15 KO mice compared to WT mice.
399 25617474 HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.
400 25617474 In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12.
401 25617474 In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710.
402 25617474 Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease).
403 25617474 Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease.
404 25780036 CD4+ T cell-derived IL-21 and deprivation of CD40 signaling favor the in vivo development of granzyme B-expressing regulatory B cells in HIV patients.
405 25780036 In this article, we demonstrate that untreated HIV patients display CD4(+) T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B.
406 25780036 Granzyme B-expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10.
407 25780036 Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L.
408 25780036 When culturing such IL-21(+)CD40L(-) Th cells with B cells, the former directly induce B cell differentiation into GraB cells.
409 25780036 In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21-dependent B cell differentiation.
410 25780036 CD4+ T cell-derived IL-21 and deprivation of CD40 signaling favor the in vivo development of granzyme B-expressing regulatory B cells in HIV patients.
411 25780036 In this article, we demonstrate that untreated HIV patients display CD4(+) T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B.
412 25780036 Granzyme B-expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10.
413 25780036 Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L.
414 25780036 When culturing such IL-21(+)CD40L(-) Th cells with B cells, the former directly induce B cell differentiation into GraB cells.
415 25780036 In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21-dependent B cell differentiation.
416 25780036 CD4+ T cell-derived IL-21 and deprivation of CD40 signaling favor the in vivo development of granzyme B-expressing regulatory B cells in HIV patients.
417 25780036 In this article, we demonstrate that untreated HIV patients display CD4(+) T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B.
418 25780036 Granzyme B-expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10.
419 25780036 Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L.
420 25780036 When culturing such IL-21(+)CD40L(-) Th cells with B cells, the former directly induce B cell differentiation into GraB cells.
421 25780036 In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21-dependent B cell differentiation.
422 25844718 Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects.
423 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.
424 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.
425 25849837 Results showed that, after three doses of vaccine, central memory and effector memory CD4(+) and CD8(+) T lymphocytes, as well as HPV-specific interleukin (IL)2(+)/CD4(+), interferon-gamma (IFN-γ(+))/CD4(+), IFN-γ(+)/CD8(+) and tumour necrosis factor-alpha (TNF-α)(+)/CD8(+) T lymphocytes and Perforin and Granzyme B secreting CD8(+) T lymphocytes were significantly increased.
426 25874544 To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNγ-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells (Bexhaust).
427 25874544 IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg.
428 25898266 Mouse immunization with pH-responsive PLGA NPs induced greater lymphocyte activation, more antigen-specific CD8(+) T cells, stronger cytotoxic capacity (IFN-γ and granzyme B), enhanced antigen-specific IgG antibodies, and higher serum IgG2a/IgG1, indicating cellular immunity.
429 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.
430 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.
431 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.
432 25960935 Molecular mimicry of MAGE-A6 and Mycoplasma penetrans HF-2 epitopes in the induction of antitumor CD8+ T-cell responses.
433 25960935 A promising vaccine strategy for the treatment of cancer involves the use of vaccines incorporating tumor antigen-derived synthetic peptides that can be coordinately recognized by specific CD4+ and CD8+ T-cells.
434 25960935 Previously, we reported that a MAGE-A6-derived peptide (MAGE-A6172-187) and its highly-immunogenic and cross-reactive homolog derived from Mycoplasma penetrans HF-2 permease (HF-2216-229) are promiscuously presented by multiple HLA-DR alleles to responder CD4+ T-cells obtained from healthy donors and melanoma patients.
435 25960935 Here, we investigated whether these same peptides could concomitantly stimulate cross-reactive MAGE-A6-specific CD8+ T-cell responses in vitro using cells isolated from HLA-A*0201 (HLA-A2)+ healthy individuals and patients with melanoma.
436 25960935 We now show that MAGE-A6172-187 and, even more so, HF-2216-229, induce memory CD8+ T cells that recognize HLA-A2+ MAGE-A6+ tumor target cells.
437 25960935 The immunogenicity of these peptides was at least partially attributed to their embedded MAGE-A6176-185 and HF-2220-229 "homologous" sequences.
438 25960935 The functional avidity of HF-2216-229 peptide-primed CD8+ T cells for the MAGE-A6172-187 peptide was more than 100-fold greater than that of CD8+ T cells primed with the corresponding MAGE-A6 peptide.
439 25960935 Additionally, these 2 peptides were recognized in interferon γ (IFNγ) and granzyme B ELISPOT assays by CD8+ T-cell clones displaying variable T-cell receptor (TCR) Vβ usage.
440 25960935 These data suggest that the immune cross-reactivity of the MAGE-A6172-187 and HF-2216-229 peptides extends to CD8+ T cells, at least in HLA-A2+ donors, and supports the potential translational utility of these epitopes in clinical vaccine formulations and for immunomonitoring of cancer patients.
441 25999171 We demonstrate that both resting and activated B-cells process and present antigens delivered via mechano-poration exclusively to antigen-specific CD8(+)T-cells, and not CD4(+)T-cells.
442 25999171 Squeezed B-cells primed and expanded large numbers of effector CD8(+)T-cells in vitro that produced effector cytokines critical to cytolytic function, including granzyme B and interferon-γ.
443 26071876 Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells.
444 26071876 Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells.
445 26071876 Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished.
446 26084026 Quiescence of Memory CD8(+) T Cells Is Mediated by Regulatory T Cells through Inhibitory Receptor CTLA-4.
447 26084026 Loss of Treg cells resulted in activation of genome-wide transcriptional programs characteristic of effector T cells and drove transitioning as well as established memory CD8(+) T cells toward terminally differentiated KLRG-1(hi)IL-7Rα(lo)GzmB(hi) phenotype, with compromised metabolic fitness, longevity, polyfunctionality, and protective efficacy.
448 26084026 These studies present the CTLA-4-CD28-CD80/CD86 axis as a potential target to accelerate vaccine-induced immunity and improve T cell memory quality in current cancer immunotherapies proposing transient Treg cell ablation.
449 26133045 A single immunization of mice with replication incompetent recombinant adenovirus vectors encoding for F or core antigens induces poor T cell responses and leads to generation of CD4+ and CD8+ T cells with low granzyme B (GrB) expression.
450 26133045 Addition of exogenous IL-2 in in vitro cultures leads to partial recovery of GrB production, whereas immunization with the Toll-like receptor (TLR) agonist poly I:C leads to complete restoration of GrB expression in both CD4+ and CD8+ T cells.
451 26155399 Akt1 and -2 inhibition diminishes terminal differentiation and enhances central memory CD8+ T-cell proliferation and survival.
452 26155399 The differentiation of CD8 + memory T cells is thought to be coordinated by the phosphoinositide 3-kinase (PI3K)/Akt pathway.
453 26155399 We, therefore, investigated the role of Akt isoforms in the differentiation and proliferation of memory CD8 + T cells.
454 26155399 We found that Akt1 and Akt2, but not Akt3, drive the terminal differentiation of CD8 + T cells, and their inhibition enhances the therapeutically superior TCM phenotype.
455 26155399 Furthermore, the inhibition of Akt1 and Akt2, but not Akt 3, delays CD8 + T-cell exhaustion and preserves naïve and TCM CD8 + T cells, thus enhancing their proliferative ability and survival and prolonging their cytokine and Granzyme B production ability.
456 26155399 Here, we define a mechanism in which proliferative potential, function, and survival of CD8 + T cells are enhanced by maintaining a reservoir of TCM and naïve cells using only Akt1 and Akt2 inhibition.
457 26155399 Therefore, our findings strongly suggest the utility of using Akt1 and Akt2 inhibitors to modulate CD8 + T cells, both for adoptive cell transfer and vaccine-based cancer immune therapies.
458 26191409 We recently reported that human B cells from healthy donors secrete active GzmB when stimulated in vitro through B-cell receptor (BCR) ligation and interleukin (IL)-21.
459 26194553 In addition to type I interferons, TRAIL and granzyme B contributed to the inhibitory effect of HSV-1 d106S plus pDC to a minor extent.
460 26195744 Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity.
461 26195744 Although DENV-specific CD8(+) T-cell responses have been extensively studied, the breadth and specificity of CD4(+) T-cell responses remains to be defined.
462 26195744 Ex vivo flow-cytometric analysis of DENV-specific CD4(+) T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1(+) Eomesodermin(+) perforin(+) granzyme B(+) CD45RA(+) CD4 CTL phenotype.
463 26228786 Molecular characterization of HCMV-specific immune responses: Parallels between CD8(+) T cells, CD4(+) T cells, and NK cells.
464 26228786 The HCMV-specific CD8(+) T-cell response is characterized by the accumulation of terminally differentiated effector cells that have downregulated the costimulatory molecules CD27 and CD28.
465 26228786 These HCMV-specific CD8(+) T cells maintain high levels of cytotoxic molecules such as granzyme B and rapidly produce the inflammatory cytokine IFN-γ upon activation.
466 26228786 HCMV also induces the differentiation of effector CD4(+) T cells and NK cells, which share characteristics with HCMV-specific CD8(+) T cells.
467 26228786 We propose that the overlap in differentiation of NK cells, CD4(+) and CD8(+) T cells after HCMV infection may be regulated by a shared transcriptional machinery.
468 26278150 In this study, by using glutaraldehyde cross-linking, we constructed a potential therapeutic peptide vaccine, heat shock protein 72 (HSP72) and AFP epitope peptide (HSP72/AFP-P).
469 26278150 ELISPOT was applied to evaluate the quantity of AFP-specific CD8+ T cell that secreted IFN-γ in immunized BALB/C mice.
470 26278150 Granzyme B released from natural killer cells and AFP-specific antibody responses in immunized mice were detected by ELISA.
471 26278150 The results showed that reconstructed HSP72 and AFP epitope peptide vaccine synergistically exhibited significant increases in AFP-specific CD8+ T cells, natural killer cells responses and impressive antitumor effects against AFP-expressing tumors.
472 26278150 The numbers of IFN-γ-producing CD8+ T cells from mice immunized with HSP72/AFP-P were 30 times more than those from mice immunized with AFP-P, HSP72 or PBS (P < 0.01).
473 26278150 The concentration of granzyme B in natural killer cells from mice immunized with HSP72/AFP-P were 15 times higher than that from other groups (P < 0.01).
474 26278150 Our study suggests that constructing a tumor vaccine by cross-linking AFP antigen epitope peptide and HSP72 is a promising approach for cancer therapy.
475 26278150 In this study, by using glutaraldehyde cross-linking, we constructed a potential therapeutic peptide vaccine, heat shock protein 72 (HSP72) and AFP epitope peptide (HSP72/AFP-P).
476 26278150 ELISPOT was applied to evaluate the quantity of AFP-specific CD8+ T cell that secreted IFN-γ in immunized BALB/C mice.
477 26278150 Granzyme B released from natural killer cells and AFP-specific antibody responses in immunized mice were detected by ELISA.
478 26278150 The results showed that reconstructed HSP72 and AFP epitope peptide vaccine synergistically exhibited significant increases in AFP-specific CD8+ T cells, natural killer cells responses and impressive antitumor effects against AFP-expressing tumors.
479 26278150 The numbers of IFN-γ-producing CD8+ T cells from mice immunized with HSP72/AFP-P were 30 times more than those from mice immunized with AFP-P, HSP72 or PBS (P < 0.01).
480 26278150 The concentration of granzyme B in natural killer cells from mice immunized with HSP72/AFP-P were 15 times higher than that from other groups (P < 0.01).
481 26278150 Our study suggests that constructing a tumor vaccine by cross-linking AFP antigen epitope peptide and HSP72 is a promising approach for cancer therapy.
482 26363059 Additionally, gB-specific CD4(+) T cells exhibited a more cytotoxic phenotype, with high levels of granzyme B expression.
483 26405163 C-ter-J28+-DC-vaccinations selectively enhanced cell immunoreactivity to Panc02, as demonstrated by CD4+- and CD8+-T-cell activation, increased percentages of CD4+- and CD8+-T-cells and NK1.1+ cells expressing granzyme B, and T-cell cytotoxicity.
484 26420714 In peripheral blood mononuclear cells (PBMC) challenged with live influenza virus, an increase in the interferon-γ:interleukin-10 (IFN-γ:IL-10) ratio and the level of the cytolytic mediator, granzyme B (GrzB), correlates with protection against influenza in vaccinated older adults.