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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.

Original publication

DOI

10.1002/1521-4141(200103)31:3<677::AID-IMMU677>3.0.CO;2-M

Type

Journal article

Journal

Eur J Immunol

Publication Date

03/2001

Volume

31

Pages

677 - 686

Keywords

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