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Title

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

Authors
Oxenius, A.
Gunthard, Huldrych
Fidler, S.
Weber, J. N.
Easterbrook, P. J.
Bell, J. I.
Phillips, R. E.
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Published in European Journal of Immunology. 2001, vol. 31, no. 4, p. 1115-1121
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/analysisAnti-HIV Agents/pharmacology/therapeutic useAntigens, CD8/metabolismApoptosis/drug effectsCD8-Positive T-Lymphocytes/drug effects/ immunology/metabolismCells, CulturedChronic DiseaseDown-Regulation/drug effectsFlow CytometryHIV Infections/ drug therapy/ immunology/virologyHIV-1/drug effects/ immunology/physiologyHistocompatibility Antigens Class I/immunologyHumansImmunophenotypingLymphocyte Activation/drug effectsPeptides/immunologyReceptors, Antigen, T-Cell/metabolismViral Load
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PMID: 11298336
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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. https://archive-ouverte.unige.ch/unige:7455

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Deposited on : 2010-06-21

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