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Expansion of hepatitis C-specific CD4+CD25+ regulatory T cells after viral clearance: a mechanism to limit collateral damage?

Godkin, Andrew James, Ng, Wan Fai, Gallagher, Kathleen M., Betts, Gareth J., Thomas, Howard C. and Lechler, Robert I. 2008. Expansion of hepatitis C-specific CD4+CD25+ regulatory T cells after viral clearance: a mechanism to limit collateral damage? Journal of Allergy and Clinical Immunology 121 (5) , pp. 1277-1284. 10.1016/j.jaci.2008.01.070

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Abstract

Background Data from rodent models suggest that a subpopulation of CD4+ T cells, characterized by the constitutive expression of CD25, play a key role in regulating many immune responses. Human CD4+CD25+ T cells also appear to possess a regulatory function, but their role in infections is not fully defined. Objectives We sought to explore the possibility of a role for CD4+CD25+ T cells in controlling immunity to hepatitis C virus (HCV). We hypothesized that CD4+CD25+ T cells might account for the paucity of immune responses measurable in chronically viremic patients by suppressing the immune responses to HCV antigens. Methods We compared the responses of PBMCs to 3 different recombinant HCV antigens before and after depletion of CD25+ cells in 15 chronically viremic patients, 14 nonviremic HCV antibody–positive subjects, and 14 healthy control subjects. We also tested the ability of CD4+CD25+ T cells purified from HLA-matched viremic or nonviremic blood to suppress the responses of HCV epitope–specific T-cell clones. Results To our surprise, depletion of peripheral blood CD25+ cells led to a pronounced increase in proliferation of and IFN-γ production by PBMCs only in nonviremic patients. Furthermore, the CD4+CD25+ T cells purified from HLA-matched nonviremic blood (in contrast to CD4+CD25+ T cells isolated from chronically viremic blood) inhibited the responses of HCV epitope–specific T-cell clones. Conclusion HCV-specific CD4+CD25+ regulatory T cells appear to accompany successful viral clearance.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: hepatitis C infection, regulatory T cells, autoimmunity, viral clearance, viral persistence
Publisher: Elsevier
ISSN: 0091-6749
Last Modified: 23 Oct 2017 09:04
URI: http://orca.cf.ac.uk/id/eprint/25710

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