scholarly journals Human CD14+CTLA-4+regulatory dendritic cells suppress T-cell response by cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase production in hepatocellular carcinoma

Hepatology ◽  
2013 ◽  
Vol 59 (2) ◽  
pp. 567-579 ◽  
Author(s):  
Yanmei Han ◽  
Zhubo Chen ◽  
Yuan Yang ◽  
Zhengping Jiang ◽  
Yan Gu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dendritic Cells ◽  
T Cell ◽  
T Lymphocyte ◽  
Cell Response ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response ◽  
Lymphocyte Antigen ◽  
Indoleamine 2,3 Dioxygenase ◽  
Regulatory Dendritic Cells

scholarly journals Dendritic Cell-Secreted Cytotoxic T-Lymphocyte-Associated Protein-4 Regulates the T-cell Response by Downmodulating Bystander Surface B7

2016 ◽  
Vol 25 (10) ◽  
pp. 774-787 ◽  
Author(s):  
Matthew M. Halpert ◽  
Vanaja Konduri ◽  
Dan Liang ◽  
Yunyu Chen ◽  
James B. Wing ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Lymphocyte ◽  
Cell Response ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response

scholarly journals Cytotoxic T-Lymphocyte Antigen 4 Gene and Recovery from Hepatitis B Virus Infection

2004 ◽  
Vol 78 (20) ◽  
pp. 11258-11262 ◽  
Author(s):  
Chloe L. Thio ◽  
Timothy L. Mosbruger ◽  
Richard A. Kaslow ◽  
Christopher L. Karp ◽  
Steffanie A. Strathdee ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Lymphocyte ◽  
Cell Response ◽  
Cytotoxic T Lymphocyte ◽  
Viral Persistence ◽  
T Cell Response ◽  
Hbv Infection ◽  
B Virus

ABSTRACT Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory T-cell receptor expressed by activated and regulatory T cells. We hypothesized that single-nucleotide polymorphisms (SNPs) in the gene encoding CTLA-4 may affect the vigor of the T-cell response to hepatitis B virus (HBV) infection, thus influencing viral persistence. To test this hypothesis, we genotyped six CTLA4 SNPs, from which all frequent haplotypes can be determined, using a large, matched panel of subjects with known HBV outcomes. Haplotypes with these SNPs were constructed for each subject using PHASE software. The haplotype distribution differed between those with viral persistence and those with clearance. Two haplotypes were associated with clearance of HBV infection, which was most likely due to associations with the SNPs −1722C (odds ratio [OR] = 0.60, P = 0.06) and +49G (OR = 0.73, P = 0.02). The wild-type haplotype, which contains an SNP leading to a decreased T-cell response (+6230A), was associated with viral persistence (OR = 1.32, P = 0.04). These data suggest that CTLA4 influences recovery from HBV infection, which is consistent with the emerging role of T regulatory cells in the pathogenesis of disease.

scholarly journals Acute Resolving Woodchuck Hepatitis Virus (WHV) Infection Is Associated with a Strong Cytotoxic T-Lymphocyte Response to a Single WHV Core Peptide

2007 ◽  
Vol 81 (13) ◽  
pp. 7156-7163 ◽  
Author(s):  
Ina Frank ◽  
Claudia Budde ◽  
Melanie Fiedler ◽  
Uta Dahmen ◽  
Sergei Viazov ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cell Response ◽  
Cytotoxic T Lymphocyte ◽  
Hepatitis Virus ◽  
Immunological Response ◽  
T Cell Response ◽  
Woodchuck Hepatitis Virus ◽  
Core Peptide ◽  
Ctl Responses

ABSTRACT Woodchucks infected with woodchuck hepatitis virus (WHV) are an excellent model for studying acute, self-limited and chronic hepadnaviral infections. Defects in the immunological response leading to chronicity are still unknown. Specific T-helper cell responses to WHV core and surface antigens (WHcAg and WHsAg, respectively) are associated with acute resolving infection; however, they are undetectable in chronic infection. Up to now, cytotoxic T-lymphocyte (CTL) responses could not be determined in the woodchuck. In the present study, we detected virus-specific CTL responses by a CD107a degranulation assay. The splenocytes of woodchucks in the postacute phase of WHV infection (18 months postinfection) were isolated and stimulated with overlapping peptides covering the whole WHcAg. After 6 days, the cells were restimulated and stained for CD3 and CD107a. One peptide (c96-110) turned out to be accountable for T-cell expansion and CD107a staining. Later, we applied the optimized degranulation assay to study the kinetics of the T-cell response in acute WHV infection. We found a vigorous T-cell response against peptide c96-110 with peripheral blood cells beginning at the peak of viral load (week 5) and lasting up to 15 weeks postinfection. In contrast, there was no T-cell response against peptide c96-110 detectable in chronically WHV-infected animals. Thus, with this newly established flow cytometric degranulation assay, we detected for the first time virus-specific CTLs and determined one immunodominant epitope of WHcAg in the woodchuck.

Regulatory dendritic cells program B cells to differentiate into CD19hiFcγIIbhi regulatory B cells through IFN-β and CD40L

Blood ◽  
2012 ◽  
Vol 120 (3) ◽  
pp. 581-591 ◽  
Author(s):  
Li Qian ◽  
Cheng Qian ◽  
Yongjian Chen ◽  
Yi Bai ◽  
Yan Bao ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Response ◽  
T Cell Response ◽  
Peripheral Tolerance ◽  
Regulatory Function ◽  
Regulatory B Cells ◽  
Regulatory Dendritic Cells

Abstract Regulatory dendritic cells (DCs) play important roles in the induction of peripheral tolerance and control of adaptive immune response. Our previous studies demonstrate that splenic stroma can drive mature DCs to proliferate and further differentiate into a unique subset of CD11bhiIalow regulatory DCs, which could inhibit T-cell response, program generation of immunosuppressive memory CD4 T cells. However, the effect of regulatory DCs on B-cell function remains unclear. Here, we report that regulatory DCs can induce splenic B cells to differentiate into a distinct subtype of IL-10–producing regulatory B cells with unique phenotype CD19hiFcγIIbhi. CD19hiFcγIIbhi B cells inhibit CD4 T-cell response via IL-10. CD19hiFcγIIbhi B cells have enhanced phagocytic capacity compared with conventional CD19+ B cells, and FcγRIIb mediates the uptake of immune complex by CD19hiFcγIIbhi B cells. We found that regulatory DC-derived IFN-β and CD40 ligand are responsible for the differentiation of CD19hiFcγIIbhi B cells. Furthermore, an in vivo counterpart of CD19hiFcγIIbhi B cells in the spleen and lymph nodes with similar phenotype and regulatory function has been identified. Our results demonstrate a new manner for regulatory DCs to down-regulate immune response by, at least partially, programming B cells into regulatory B cells.

scholarly journals Cytotoxic T Lymphocyte Antigen Costimulation Influences T-Cell Activation in Response to Cryptococcus neoformans

2001 ◽  
Vol 69 (3) ◽  
pp. 1508-1514 ◽  
Author(s):  
Donatella Pietrella ◽  
Stefano Perito ◽  
Francesco Bistoni ◽  
Anna Vecchiarelli
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cryptococcus Neoformans ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
T Cell Response ◽  
Lymphocyte Antigen

ABSTRACT The kinetics of cytotoxic T lymphocyte antigen 4 (CTLA-4) expression on T cells responding to Cryptococcus neoformansand its role in regulating the T-cell response were examined. Using peripheral blood mononuclear cells stimulated with encapsulated or acapsular C. neoformans we showed that (i) the encapsulated strain augmented CTLA-4 expression on the T-cell surface while the acapsular strain was a weaker modulator, (ii) CTLA-4 molecules were rapidly up-regulated after the addition of encapsulated C. neoformans, (iii) CTLA-4 was up-regulated predominantly in CD4+ T cells responding to C. neoformans, and (iv) blockage of CTLA-4 with (Fab′)2 of monoclonal antibody to CTLA-4 induced T-cell proliferation that paralleled the enhancement of interleukin-2 and gamma interferon production. These results suggest that capsular material, the major virulence factor of C. neoformans, promotes synthesis and expression of CTLA-4 molecules predominantly in CD4+ T cells. CTLA-4-mediated deactivation is due not to lack of costimulation but to specific recognition of CTLA-4 for B7 molecules. This appears to be a new mechanism by whichC. neoformans may elude the host immune response.

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