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

Background. Human immunodeficiency virus (HIV) coinfection and low peripheral blood CD4 super(+) T cell counts are associated with increased hepatitis C liver disease. Methods. Hepatitis C virus (HCV)-specific CD4 super(+) T cell responses were assessed using interferon (IFN)- gamma enzyme-linked im...

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Published in:The Journal of infectious diseases Vol. 196; no. 4; pp. 577 - 586
Main Authors: Morishima, C, Shuhart, M C, Yoshihara, C S, Paschal, D M, Silva, MA, Thomassen, U V, Emerson, S S, Gretch, DR
Format: Journal Article
Language:English
Published: 15-08-2007
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Summary:Background. Human immunodeficiency virus (HIV) coinfection and low peripheral blood CD4 super(+) T cell counts are associated with increased hepatitis C liver disease. Methods. Hepatitis C virus (HCV)-specific CD4 super(+) T cell responses were assessed using interferon (IFN)- gamma 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 super(+) 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 super(+) T ceils 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 super(+) T cells (P = .4). Circulating and liver CD4 super(+) 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 super(+) T cell percentages nor HCV-specific IFN- gamma responses in the liver or periphery predicted stage. Conclusions. Despite decreases in peripheral blood HCV-specific CD4 super(+) T cell responses and intrahepatic CD4 super(+) T cell percentages, intrahepatic HCV-specific CD4 super(+) IFN- gamma responses were preserved in HCV/HIV coinfection.
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ISSN:0022-1899
DOI:10.1086/519386