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Stronger hepatitis C virus-specific CD8+ T-cell responses in HIV coinfection
L Barrett1, M Gallant, C Howley
1Immunology Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada. lisa.barrett@dal.ca
Insights
Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) accelerates liver disease. While HIV reduces T-cell responses, stronger CD8+ T-cell activity against HCV was observed in coinfected individuals.
Area of Science:
- Immunology
- Virology
- Hepatology
Background:
- Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share transmission routes, leading to frequent coinfection.
- HIV coinfection accelerates liver disease progression in HCV-infected individuals compared to HCV monoinfection.
- The immunological mechanisms behind accelerated liver disease in HIV/HCV coinfection remain unclear.
Purpose of the Study:
- To compare T-cell responses (CD4+ and CD8+) in HIV/HCV coinfection versus HCV monoinfection.
- To investigate how anti-HCV antibody and HCV RNA status influence immune responses in coinfection.
- To elucidate the role of the immune system in the accelerated liver disease pathogenesis.
Main Methods:
- Comparison of peripheral blood CD4+ and CD8+ T-cell responses' frequency, magnitude, breadth, and specificity.
- Analysis of T-cell responses in HCV-monoinfected and HIV/HCV-coinfected individuals.
- Subgroup analysis based on anti-HCV antibody and HCV RNA status.
Main Results:
- HIV coinfection generally reduced the frequency and breadth of anti-HCV CD8+ T-cell responses but increased their strength when present.
- HCV-specific CD4+ T-cell responses were rare and weak across all groups, irrespective of HIV status or CD4+ counts.
- HIV/HCV-coinfected individuals without anti-HCV antibodies showed restricted CD8+ T-cell response breadth and lower B-cell counts.
- Significantly stronger HCV-specific CD8+ T-cell responses were found in HIV/HCV-coinfected individuals compared to HCV-monoinfected individuals.
Conclusions:
- Stronger HCV-specific CD8+ T-cell responses in HIV/HCV coinfection may contribute to accelerated liver disease.
- Immune dysregulation in HIV/HCV coinfection impacts viral-specific T-cell dynamics.
- Further research is needed to fully understand the immune interplay and its clinical consequences.
Abstract:
Hepatitis C virus (HCV) is a widespread chronic infection that shares routes of transmission with human immunodeficiency virus (HIV). Thus, coinfection with these viruses is a relatively common and growing problem. In general, liver disease develops over years with HIV coinfection, when compared to decades in HCV monoinfection. The role of the immune system in the accelerated pathogenesis of liver disease in HIV/HCV coinfection is not clear. In this study, we compared the frequency, magnitude, breadth and specificity of peripheral blood CD4+ and CD8+ T-cell responses between HCV-monoinfected and HCV/HIV-coinfected individuals and between HIV/HCV-coinfected subgroups distinguished by anti-HCV antibody and HCV RNA status. While HIV coinfection tended to reduce the frequency and breadth of anti-HCV CD8+ T-cell responses in general, responses that were present were substantially stronger than in monoinfection. In all groups, HCV-specific CD4+ T-cell responses were rare and weak, independent of either nadir or concurrent CD4+ T-cell counts of HIV-infected individuals. Subgroup analysis demonstrated restricted breadth of CD8+ HCV-specific T-cell responses and lower B-cell counts in HIV/HCV-coinfected individuals without anti-HCV antibodies. The greatest difference between HIV/HCV-coinfected and HCV-monoinfected groups was substantially stronger HCV-specific CD8+ T-cell responses in the HIV-coinfected group, which may relate to accelerated liver disease in this setting.
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