Preservation of Intrahepatic Hepatitis C Virus (HCV)–Specific CD4+T Cell Responses despite Global Loss of CD4+T Cells in HCV/HIV Coinfection

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Abstract
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%; P < .0001) and liver (15% vs. 36%; P < .0001) and with reduced responsiveness of peripheral CD4+ T cells to HCV antigens compared with HCV monoinfection (22% vs. 45%; P = .021). However, intrahepatic HCV-specific responses were maintained in HCV/HIV coinfection, compared with HCV monoinfection (38% vs. 32%; P = .7). Notably, the presence of HCV-specific responses was not related to the frequency of liver CD4+ T cells (P = .4). Circulating and liver CD4+ T cell percentages were correlated (r = 0.58; P < .0001). Circulating percentages were also inversely associated with liver fibrosis stage among HCV/HIV-coinfected subjects (P = .029). 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.

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