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NLM AIDSLINE

Apoptosis associated with ex vivo down-regulation of Bcl-2 and up-regulation of Fas in potential cytotoxic CD8+ T lymphocytes during HIV infection.




 

J Immunol. 1996 Mar 15;156(6):2282-93. Unique Identifier : AIDSLINE

In this study, we have investigated whether the enhanced apoptosis of CD4+ and CD8+ T lymphocytes throughout HIV infection was controlled by the bcl-2 proto-oncogene, an inhibitor of programmed cell death (PCD) in mammals. We have analyzed the intracellular expression of the Bcl-2 protein by flow cytometry in freshly isolated peripheral T cells from HIV-infected and noninfected individuals. While no decrease in Bcl-2 expression was detected in the CD4+ T cell subset from the seropositive donors, a reduced level of Bcl-2 was found in a fraction of CD8+ T lymphocytes, with the proportion of these cells increasing as HIV infection progressed. We show that the low Bcl-2-expressing CD8+ T cells were highly susceptible to spontaneous apoptosis upon short term culture. Interestingly, PCD significantly increased when these lymphocytes were cultured in the presence of a Fas-specific mAb, which was related to the high expression of the Fas Ag on their surface. The low Bcl-2 CD8+ subpopulation displayed activation markers CD45RO, HLA-DR, and CD38 and expressed TIA-1-positive, but perforin-negative, granules, while lacking the CD28 Ag. These observations suggest that such low Bcl-2 CD8+ T cells correspond to either immature or end-staged anergic CTLs. Moreover, they indicate that down-regulation of Bcl-2 and up-regulation of Bcl-2 and up-regulation of Fas in CD8+ T lymphocytes, associated with the chronic stimulation of these cells during HIV infection, might render them sensitive to Fas-mediated PCD. Such a Bcl-2/Fas-regulated apoptosis could be responsible for the disappearance of both memory CD45RO+ T cell response and HIV-specific cytotoxic activity occurring in the course of HIV infection and could contribute to AIDS pathogenesis.

Antigens, CD95/*BIOSYNTHESIS/PHYSIOLOGY Apoptosis/*IMMUNOLOGY Cells, Cultured Down-Regulation (Physiology)/*IMMUNOLOGY Human HIV Infections/*IMMUNOLOGY/PATHOLOGY Immune Tolerance Immunologic Memory Immunophenotyping Lymphocyte Transformation Proto-Oncogene Proteins/*BIOSYNTHESIS Support, Non-U.S. Gov't T-Lymphocytes, Cytotoxic/CLASSIFICATION/*IMMUNOLOGY/METABOLISM Up-Regulation (Physiology)/*IMMUNOLOGY JOURNAL ARTICLE



 




Information in this article was accurate in October 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.