Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 40, Issue 9, Pages 2493-2505Publisher
WILEY
DOI: 10.1002/eji.201040340
Keywords
Hepatitis C; HIV; T-cell exhaustion
Categories
Funding
- Canadian Institute for Health Research (CIHR)
- Fonds de recherche en sante du Quebec
- Reseau SIDA/maladies infectieuses
- Canadian HIV Trials Network [CTN222]
- Ontario HIV Treatment Network (OHTN)
- National Canadian Research Training Program (NCRTP) in Hepatitis C
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Co-infection of HCV with HIV has been associated with more rapid progression of HCV-related disease. HCV-specific T-cell immune responses, which are essential for disease control, are attenuated in co-infection with HIV. T-cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) expression in T-cell exhaustion during HCV/HIV co-infection. We show that in HCV/HIV co-infection, both total and HCV-specific T cells co-express Tim-3 and PD-1 in significantly higher frequencies, compared with HCV mono-infection. Co-expression of these two markers on HCV-specific CD8(+) T cells positively correlated with a clinical parameter of liver disease progression. HCV-specific CD8(+) T cells showed greater frequencies of Tim-3/PD-1 co-expression than HIV-specific CD8(+) T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim-3 or PD-1 pathways restored both HIV- and HCV-specific CD8(+) T-cell expansion in the blood of co-infected individuals. These data demonstrate that co-expression of Tim-3 and PD-1 ay play a significant role in HCV-specific T-cell dysfunction, especially in the setting of HIV co-infection.
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