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. 2005 Feb 1;105(3):1170-8. doi: 10.1182/blood-2004-06-2336. Epub 2004 Sep 30.

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-gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology*
  • Adult
  • Biopsy
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology*
  • Cytokines / analysis
  • Female
  • Genotype
  • HIV Infections / immunology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepacivirus / isolation & purification
  • Hepatitis C / immunology*
  • Histocompatibility Testing
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • RNA, Viral / genetics
  • Viral Load

Substances

  • Cytokines
  • RNA, Viral