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


OBJECTIVE
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-gamma 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.


CONCLUSIONS
HCV-specific CD4+CD25+ regulatory T cells appear to accompany successful viral clearance.
Godkin
Andrew
A
Department of Medicine, Imperial College, St Mary's Campus, London, United Kingdom.
Ng
Wan Fai
WF
Gallagher
Kathleen
K
Betts
Gareth
G
Thomas
Howard C
HC
Lechler
Robert I
RI
D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology*; D018937:Hepatitis C Antibodies / Q000097:blood / Q000276:immunology; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000276:immunology
D016207:Cytokines; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens