Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

An immunomodulatory role for CD4 + CD25 + regulatory T lymphocytes in hepatitis C virus infection

An immunomodulatory role for CD4 + CD25 + regulatory T lymphocytes in hepatitis C virus infection The CD4+CD25+ regulatory T lymphocytes have been implicated in suppressing T cell immune responses. Our aim was to characterize the frequency, phenotype, function, and specificity of CD4+CD25+ T cells in hepatitis C virus (HCV) infection. Peripheral CD4+CD25+ cells from recovered (n = 15), chronic infected (n = 30), and normal control (n = 15) subjects were analyzed ex vivo for quantitation, phenotype, and effect on HCV‐specific interferon gamma production and proliferation. CD4+CD25+ specificity was determined by intracellular cytokine staining for interleukin 10 (IL‐10). A higher proportion of CD4+CD25+ were found in chronic infection (mean, 3.02%) when compared with recovered (1.64%, P = .001) and normal controls (2.27%, P = .02). CD4+CD25+ cells display CD45ROhigh, CD45RAlow, CD28high, CD62Lhigh, and CD95high phenotype. HCV‐specific interferon gamma activity was enhanced in peripheral blood mononuclear cells depleted of CD4+CD25+ and suppressed in peripheral blood mononuclear cells enriched with CD4+CD25+. Depletion of CD4+CD25+ cells also enhanced HCV‐specific CD4+ and CD8+ T cell proliferation. Cytokine analysis suggested CD4+CD25+ cells secrete transforming growth factor beta (TGF‐β1) and IL‐10. The inhibitory role for TGF‐β1 was confirmed by anti–TGF‐β1. Transwell studies showed CD4+CD25+ mediated suppression to be dose dependent and requiring cell contact. CD4+CD25+ cells showed HCV‐specificity through IL‐10 production, with a frequency ranging from 1.9% to 5.3%. A positive correlation was detected between CD4+CD25+ T cell frequency and HCV RNA titer, whereas an inverse relation was found with liver inflammatory activity. In conclusion, CD4+CD25+ T lymphocytes constitute a highly differentiated population and appear to play a role in viral persistence by suppressing HCV‐specific T cell responses in a cell–cell contact manner. (HEPATOLOGY 2004;40:1062–1071.) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hepatology Wiley

An immunomodulatory role for CD4 + CD25 + regulatory T lymphocytes in hepatitis C virus infection

Loading next page...
 
/lp/wiley/an-immunomodulatory-role-for-cd4-cd25-regulatory-t-lymphocytes-in-ooY3MR8JdG

References (42)

Publisher
Wiley
Copyright
Copyright © 2004 American Association for the Study of Liver Diseases
ISSN
0270-9139
eISSN
1527-3350
DOI
10.1002/hep.20454
pmid
15486925
Publisher site
See Article on Publisher Site

Abstract

The CD4+CD25+ regulatory T lymphocytes have been implicated in suppressing T cell immune responses. Our aim was to characterize the frequency, phenotype, function, and specificity of CD4+CD25+ T cells in hepatitis C virus (HCV) infection. Peripheral CD4+CD25+ cells from recovered (n = 15), chronic infected (n = 30), and normal control (n = 15) subjects were analyzed ex vivo for quantitation, phenotype, and effect on HCV‐specific interferon gamma production and proliferation. CD4+CD25+ specificity was determined by intracellular cytokine staining for interleukin 10 (IL‐10). A higher proportion of CD4+CD25+ were found in chronic infection (mean, 3.02%) when compared with recovered (1.64%, P = .001) and normal controls (2.27%, P = .02). CD4+CD25+ cells display CD45ROhigh, CD45RAlow, CD28high, CD62Lhigh, and CD95high phenotype. HCV‐specific interferon gamma activity was enhanced in peripheral blood mononuclear cells depleted of CD4+CD25+ and suppressed in peripheral blood mononuclear cells enriched with CD4+CD25+. Depletion of CD4+CD25+ cells also enhanced HCV‐specific CD4+ and CD8+ T cell proliferation. Cytokine analysis suggested CD4+CD25+ cells secrete transforming growth factor beta (TGF‐β1) and IL‐10. The inhibitory role for TGF‐β1 was confirmed by anti–TGF‐β1. Transwell studies showed CD4+CD25+ mediated suppression to be dose dependent and requiring cell contact. CD4+CD25+ cells showed HCV‐specificity through IL‐10 production, with a frequency ranging from 1.9% to 5.3%. A positive correlation was detected between CD4+CD25+ T cell frequency and HCV RNA titer, whereas an inverse relation was found with liver inflammatory activity. In conclusion, CD4+CD25+ T lymphocytes constitute a highly differentiated population and appear to play a role in viral persistence by suppressing HCV‐specific T cell responses in a cell–cell contact manner. (HEPATOLOGY 2004;40:1062–1071.)

Journal

HepatologyWiley

Published: Nov 1, 2004

There are no references for this article.