HIV-specific T-cells accumulate in the liver in HCV/HIV co-infection

PLoS One. 2008;3(10):e3454. doi: 10.1371/journal.pone.0003454. Epub 2008 Oct 20.

Abstract

Background and aims: Hepatitis C Virus (HCV)-related liver disease progresses more rapidly in individuals co-infected with Human Immunodeficiency Virus-1 (HIV), although the underlying immunologic mechanisms are unknown. We examined whether HIV-specific T-cells are identified in the liver of HCV/HIV co-infected individuals and promote liver inflammation through bystander immune responses.

Methods: Ex-vivo intra-hepatic lymphocytes from HCV mono-infected and HCV/HIV co-infected individuals were assessed for immune responses to HIV and HCV antigens by polychromatic flow cytometry.

Results: HCV/HIV liver biopsies had similar frequencies of lymphocytes but lower percentages of CD4+ T-cells compared to HCV biopsies. In co-infection, intra-hepatic HIV-specific CD8+ and CD4+ T-cells producing IFN-gamma and TNF-alpha were detected and were comparable in frequency to those that were HCV-specific. In co-infected individuals, viral-specific CD8+ T-cells produced more of the fibrogenic cytokine, TNF-alpha. In both mono- and co-infected individuals, intra-hepatic HCV-specific T-cells were poorly functional compared to HIV-specific T-cells. In co-infection, HAART was not associated with a reconstitution of intra-hepatic CD4+ T-cells and was associated with reduction in both HIV and HCV-specific intra-hepatic cytokine responses.

Conclusion: The accumulation of functional HIV-specific T-cells in the liver during HCV/HIV co-infection may represent a bystander role for HIV in inducing faster progression of liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / analysis
  • Bystander Effect / immunology
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cytokines / analysis
  • HIV Infections / complications*
  • HIV-1 / immunology*
  • Hepatitis C / complications*
  • Liver / immunology*
  • Liver / virology
  • Liver Diseases / etiology
  • Liver Diseases / immunology
  • Liver Diseases / virology*
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology*

Substances

  • Antigens, Viral
  • Cytokines