The magnitude and breadth of hepatitis C virus-specific CD8+ T cells depend on absolute CD4+ T-cell count in individuals coinfected with HIV-1

Kim, A.Y., Lauer, G.M., Ouchi, K., Addp, M.M., Lucas, M., Schulze zur Wiesch, J., Timm, J., Boczanowski, M., Duncan, J.E., Wurcel, A.G., Casson, D., Chung, R.T., Draenert, R., Klenerman, P. and Walker, B.D. (2004) The magnitude and breadth of hepatitis C virus-specific CD8+ T cells depend on absolute CD4+ T-cell count in individuals coinfected with HIV-1. Blood, 105 (3). pp. 1170-1178.

Abstract

CD8+ T-cell responses are an essential antiviral host defense in persistent viral infections, and their sustained effectiveness is thought to be critically dependent on CD4+ T-helper cells. To determine the relationship between HIV-1–induced CD4+ T-cell depletion and hepatitis C virus (HCV)–specific CD8+ T-cell responses during viral persistence, we studied 103 persons positive for HCV, 74 coinfected with HIV-1. CD8+ T-cell responses to the entire HCV polyprotein were determined by using an interferon-γ enzyme-linked immunospot (ELISpot) assay. Although HIV-1 infection by itself was not associated with a diminished HCV-specific response, HIV-1–associated CD4+ depletion was associated with significantly lower HCV-specific CD8+ T cells (R = 0.48, P < .0001). In contrast, declining CD4+ counts over the same range were not associated with diminished Epstein-Barr virus (EBV)– (R = 0.19, P = .31) or HIV-1–specific (R = –0.13, P = .60) CD8+ T-cell responses in persons infected with all viruses. These data indicate that frequencies of circulating HCV-specific CD8+ T-cell responses are sensitive to absolute CD4+ T-cell counts and provide a possible explanation for the accelerated HCV disease course in persons coinfected with HIV-1 and HCV.

Item Type:	Journal Article
Murdoch Affiliation(s):	Institute for Immunology and Infectious Diseases
Publisher:	American Society of Hematology
Copyright:	© American Society of Hematology
URI:	http://researchrepository.murdoch.edu.au/id/eprint/37161

Item Control Page