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

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.

journal_name

Eur J Immunol

authors

Kostense S,Ogg GS,Manting EH,Gillespie G,Joling J,Vandenberghe K,Veenhof EZ,van Baarle D,Jurriaans S,Klein MR,Miedema F

doi

10.1002/1521-4141(200103)31:3<677::aid-immu677>3.0

keywords:

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

677-86

issue

3

eissn

0014-2980

issn

1521-4141

pii

10.1002/1521-4141(200103)31:3<677::AID-IMMU677>3.0

journal_volume

31

pub_type

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