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.
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.
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, 149 13th St 5th Fl, Boston, MA 02129, USA.
Arthur Y
AY
Kim
Georg M
GM
Lauer
Kei
K
Ouchi
Marylyn M
MM
Addo
Michaela
M
Lucas
Julian
J
Schulze Zur Wiesch
Joerg
J
Timm
Melinda
M
Boczanowski
Jared E
JE
Duncan
Alysse G
AG
Wurcel
Deborah
D
Casson
Raymond T
RT
Chung
Rika
R
Draenert
Paul
P
Klenerman
Bruce D
BD
Walker
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000328:Adult; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016207:Cytokines / Q000032:analysis; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019562:Viral Load
D016207:Cytokines; D012367:RNA, Viral