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Scientific article
English

Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load

Published inEuropean Journal of Immunology, vol. 31, no. 4, p. 1115-1121
Publication date2001
Abstract

Therapeutic intervention with antiretroviral therapy (ART) enables the modulation of HIV virus load and hence provides a unique opportunity to study the consequences of varying antigen load on the phenotype of virus-specific CD8(+) T lymphocytes in a persistent human viral infection. The recent advent of tetrameric peptide / HLA class I complexes has enabled the direct phenotypic characterization of antigen-specific T cell populations ex vivo. Here, we use this technology to examine directly ex vivo the consequences of therapeutic manipulation of HIV virus load on the phenotype of HIV-specific CTL. Our observations show that: (1) distinct sequential activation patterns of CD8(+) T cells are associated with increasing virus load; (2) T cell receptor (TCR) down-regulation without apoptosis represents an early event during the generation of a T cell response in a natural infection and precedes the emergence of two distinct antigen-specific CD8(+) T cell populations which differ in TCR and CD8 expression levels. Clear differences in surface Annexin V staining were observed between these populations. The observation that CTL activation, demonstrated by TCR and CD8 down-regulation, in response to rising levels of virus load, co-segregates with apoptosis only during later stages of the response indicates that antigen-associated cell death is restricted to distinct subpopulations of CTL.

Keywords
  • Annexin A5/analysis
  • Anti-HIV Agents/pharmacology/therapeutic use
  • Antigens, CD8/metabolism
  • Apoptosis/drug effects
  • CD8-Positive T-Lymphocytes/drug effects/ immunology/metabolism
  • Cells, Cultured
  • Chronic Disease
  • Down-Regulation/drug effects
  • Flow Cytometry
  • HIV Infections/ drug therapy/ immunology/virology
  • HIV-1/drug effects/ immunology/physiology
  • Histocompatibility Antigens Class I/immunology
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation/drug effects
  • Peptides/immunology
  • Receptors, Antigen, T-Cell/metabolism
  • Viral Load
Citation (ISO format)
OXENIUS, A. et al. Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8(+) T lymphocyte activation in response to therapeutic manipulation of virus load. In: European Journal of Immunology, 2001, vol. 31, n° 4, p. 1115–1121. doi: 10.1002/1521-4141(200104)31:4<1115::AID-IMMU1115>3.0.CO;2-9
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ISSN of the journal0014-2980
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