Preservation of Intrahepatic Hepatitis C Virus (HCV)–Specific CD4+ T Cell Responses despite Global Loss of CD4+ T Cells in HCV/HIV Coinfection
Departments of 1Laboratory Medicine, 2Medicine, 3Pathology, and 4Biostatistics, University of Washington School of Medicine, Seattle
Background.
Human immunodeficiency virus (HIV) coinfection and low peripheral blood CD4+ T cell counts are associated with increased hepatitis C liver disease.
Methods.Hepatitis C virus (HCV)–specific CD4+ T cell responses were assessed using interferon (IFN)–γ enzyme‐linked immunospot assays on peripheral blood mononuclear cells and expanded liver lymphocytes from HCV‐monoinfected and HCV/HIV‐coinfected subjects. Cell frequencies were determined using flow cytometry.
Results.HIV coinfection was associated with decreased CD4+ T cell percentages in both peripheral blood (21% vs. 48%; 
) and liver (15% vs. 36%; 
) and with reduced responsiveness of peripheral CD4+ T cells to HCV antigens compared with HCV monoinfection (22% vs. 45%; 
). However, intrahepatic HCV‐specific responses were maintained in HCV/HIV coinfection, compared with HCV monoinfection (38% vs. 32%; 
). Notably, the presence of HCV‐specific responses was not related to the frequency of liver CD4+ T cells (
). Circulating and liver CD4+ T cell percentages were correlated (
; 
). Circulating percentages were also inversely associated with liver fibrosis stage among HCV/HIV‐coinfected subjects (
). Neither hepatic CD4+ T cell percentages nor HCV‐specific IFN‐γ responses in the liver or periphery predicted stage.
Conclusions.Despite decreases in peripheral blood HCV‐specific CD4+ T cell responses and intrahepatic CD4+ T cell percentages, intrahepatic HCV‐specific CD4+ IFN‐γ responses were preserved in HCV/HIV coinfection.
Received 14 November 2006; accepted 18 February 2007; electronically published 28 June 2007.
Cited by
Online publication date: 1-Jun-2008.
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Online publication date: 1-Feb-2008.
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Potential conflicts of interest: none reported.
Presented in part: 12th International Symposium on Hepatitis C Virus and Related Viruses, Montreal, Canada, 2–6 October 2005 (poster 47).
Financial support: University of Washington General Clinical Research Center (grants M01RR‐00037 and R01 AI49168‐01 to D.R.G. and and R21 AI53817‐01 to C.M.); University of Washington Center for AIDS Research, a National Institutes of Health–funded program (2004 developmental grant P30‐AI27757 to C.M.).
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Present affiliation: Washington State University, Pullman.