Direct ex vivo analysis reveals distinct phenotypic patterns of HIV-specific CD8+ T lymphocyte activation in response to therapeutic manipulation of virus load
✍ Scribed by Annette Oxenius; Huldrych F. Günthard; Bernard Hirschel; Sarah Fidler; Jonathan N. Weber; Philippa J. Easterbrook; John I. Bell; Rodney E. Phillips; David A. Price
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 138 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
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 downregulation, 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.