Affiliation:
1. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Masachusetts
2. University of Cincinnati, Cincinnati, Ohio
Abstract
ABSTRACT
Hepatitis C virus (HCV)-specific T-cell responses are rarely detected in peripheral blood, especially in the presence of human immunodeficiency virus (HIV) coinfection. Based on recent evidence that T-regulatory cells may be increased in chronic HCV, we hypothesized that functional blockade of regulatory cells could raise HCV-specific responses and might be differentially regulated in the setting of HIV coinfection. Three groups of subjects were studied: HCV monoinfected, HCV-HIV coinfected, and healthy controls. Frequencies of peripheral T cells specific for peptides derived from HCV core, HIV type 1 p24, and recall antigens were analyzed by gamma interferon (IFN-γ) enzyme-linked immunospot assay. HCV-specific T-cell responses were very weak in groups with HCV and HCV-HIV infections. Addition of blocking antibodies against transforming growth factor β1 (TGF-β1), -2, and -3 and interleukin-10 specifically increased the HCV-specific T-cell responses in both infected groups; however, this increase was attenuated in the group with HCV-HIV coinfection compared to HCV infection alone. No increase in recall antigen- or HIV-specific responses was observed. Flow cytometric sorter analysis demonstrated that regulatory-associated cytokines were produced by HCV-specific CD3
+
CD8
+
CD25
−
cells. Enhancement of the IFN-γ effect was observed for both CD4 and CD8 T cells and was mediated primarily by TGF-β1, -2, and -3 neutralization. In conclusion, blockade of TGF-β secretion could enhance peripheral HCV-specific T-cell responses even in the presence of HIV coinfection.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
91 articles.
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