High viral burden in the presence of major HIV-specific CD8(+) T cell expansions: evidence for impaired CTL effector function

Eur J Immunol. 2001 Mar;31(3):677-86. doi: 10.1002/1521-4141(200103)31:3<677::aid-immu677>3.0.co;2-m.

Abstract

To investigate the effect of HIV-specific CD8(+) T cells on viral plasma load and disease progression, we enumerated HLA-A2-, B8- and B57-restricted CD8(+) T cells directed against several HIV epitopes in a total of 54 patients by the use of tetrameric HLA-peptide complexes. In patients with high CD4(+) T cell numbers, HIV-specific tetramer(+) cells inversely correlated with viral load. Patients with CD4(+) T cell numbers below 400/microl blood, however, carried high viral load despite frequently having high tetramer(+) T cell numbers. This lack of correlation between viral load and tetramer(+) cells did not result from viral escape variants, as in only 4 of 13 patients, low frequencies of viruses with mutated epitopes were observed. In 15 patients we measured CD8(+) T cell antigen responsiveness to HIV peptide stimulation in vitro. FACS analyses showed differential IFN-gamma production of the tetramer(+) cells, and this proportion of IFN-gamma-producing tetramer(+) cells correlated with AIDS-free survival and with T cell maturation to the CD27(-) effector stage. These data show that most HIV-infected patients have sustained HIV-specific T cell expansions but many of these cells seem not to be functional, leaving the patient with high numbers of non-functional virus-specific CD8(+) T cells in the face of high viral burden.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Lymphocyte Count
  • Cells, Cultured
  • Disease Progression
  • Epitopes / genetics
  • Epitopes / immunology
  • Gene Products, nef / immunology
  • HIV Antigens / genetics
  • HIV Antigens / immunology*
  • HIV Core Protein p24 / genetics
  • HIV Core Protein p24 / immunology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HLA Antigens / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Mutation
  • Phenotype
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Load*
  • nef Gene Products, Human Immunodeficiency Virus

Substances

  • Epitopes
  • Gene Products, nef
  • HIV Antigens
  • HIV Core Protein p24
  • HLA Antigens
  • nef Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma