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Updated: Aug 23, 2026
Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV
Camilla S Graham1, Michael Curry, Qi He
1Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA. cgraham@bidmc.harvard.edu
Insights
HIV and hepatitis C coinfection accelerates liver disease progression. Coinfection alters intrahepatic interleukin-10 (IL-10) responses to hepatitis C virus (HCV) antigens, potentially driving fibrosis.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Hepatitis C virus (HCV) infection can lead to cirrhosis.
- Coinfection with human immunodeficiency virus (HIV) accelerates HCV-related liver disease progression.
- The mechanisms behind accelerated fibrosis in HIV/HCV coinfection are not fully understood.
Purpose of the Study:
- To investigate differences in intrahepatic cellular immune responses to HCV antigens between patients with HCV alone and those with HIV/HCV coinfection.
- To determine if qualitative or quantitative immune response variations contribute to increased fibrosis in coinfection.
Main Methods:
- Analysis of liver-infiltrating lymphocytes from HCV and HIV/HCV patients.
- Culture of lymphocytes with HCV antigens (core, NS3, NS5) and recall antigens.
- Measurement of cytokine secretion (IFN-gamma, TNF-alpha, IL-10) using ELISPOT assay.
Main Results:
- No significant differences in liver biopsy grade or stage between HCV and HIV/HCV groups.
- Similar secretion of IFN-gamma and TNF-alpha in response to HCV antigens between groups.
- Significantly increased IL-10 secretion in response to NS3 and NS5 antigens in HCV patients compared to HIV/HCV coinfected patients.
Conclusions:
- HIV/HCV coinfection is associated with an altered intrahepatic interleukin-10 (IL-10) cytokine response to specific HCV antigens.
- This altered IL-10 response may play a role in the accelerated progression of HCV-related liver disease observed in coinfected individuals.
Abstract:
Persons with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection are at increased risk for progression to cirrhosis compared with persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV-specific T cell destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have higher rates of fibrosis progression. We examined intrahepatic cellular immune responses to HCV antigens to determine whether there were qualitative or quantitative differences in subjects with and without HIV. Expanded, CD4-enriched, liver-infiltrating lymphocytes from 18 subjects with chronic HCV and 12 subjects with HIV/HCV were cultured in the presence of HCV core protein, nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and Candida. Secretion of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL) 10 was determined using enzyme-linked immunosorbent spot assay. There were no significant differences in liver biopsy grade or stage for HIV/HCV versus HCV groups. There were no significant differences between groups in the secretion of IFN-gamma or TNF-alpha in response to HCV or recall antigens. However, there was a significant increase in IL-10 secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and HCV coinfection. In conclusion, subjects with coinfection have an alteration of intrahepatic HCV-specific IL-10 cytokine response that may have implications for HCV-related disease progression.
