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

TY - JOUR

T1 - 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

AU - Kim, Arthur Y

AU - Lauer, Georg M

AU - Ouchi, Kei

AU - Addo, Marylyn M

AU - Lucas, Michaela

AU - Schulze Zur Wiesch, Julian

AU - Timm, Joerg

AU - Boczanowski, Melinda

AU - Duncan, Jared E

AU - Wurcel, Alysse G

AU - Casson, Deborah

AU - Chung, Raymond T

AU - Draenert, Rika

AU - Klenerman, Paul

AU - Walker, Bruce D

PY - 2005/2/1

Y1 - 2005/2/1

N2 - 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.

AB - 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.

KW - Acquired Immunodeficiency Syndrome/immunology

KW - Adult

KW - Biopsy

KW - CD4 Lymphocyte Count

KW - CD8-Positive T-Lymphocytes/immunology

KW - Cytokines/analysis

KW - Female

KW - Genotype

KW - HIV Infections/immunology

KW - HIV-1/genetics

KW - Hepacivirus/genetics

KW - Hepatitis C/immunology

KW - Histocompatibility Testing

KW - Humans

KW - Male

KW - Middle Aged

KW - RNA, Viral/blood

KW - Viral Load

U2 - 10.1182/blood-2004-06-2336

DO - 10.1182/blood-2004-06-2336

M3 - SCORING: Journal article

C2 - 15459014

VL - 105

SP - 1170

EP - 1178

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 3

ER -