Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells

Immunity. 2001 Dec;15(6):871-82. doi: 10.1016/s1074-7613(01)00246-1.

Abstract

Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8(+) T cells express the CD45RA(-)CD62L(-) but lack the CD45RA(+)CD62L(-) T cell effector memory (T(EM)) phenotype. This skewing is not found in CMV- and EBV-specific CD8(+) T cells in HIV-infected individuals. CD95/Fas-induced apoptosis is much higher in the CD45RA(-)CD62L(-) T(EM) cells. However, cytotoxicity and IFNgamma production by HIV-specific CD8(+) T cells is not impaired. Our data suggest that the survival and differentiation of HIV-specific CD8(+) T cells may be compromised by CD95/Fas apoptosis induced by FasL-expressing HIV-infected cells.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Apoptosis*
  • Cell Differentiation
  • Coculture Techniques
  • Cytomegalovirus / immunology
  • Cytotoxicity, Immunologic
  • HIV / immunology*
  • HIV Infections / immunology*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Interferon-gamma / analysis
  • L-Selectin / analysis
  • Leukocyte Common Antigens / analysis
  • Macrophages / virology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology*
  • Viral Load
  • fas Receptor / physiology*

Substances

  • fas Receptor
  • L-Selectin
  • Interferon-gamma
  • Leukocyte Common Antigens