Skip Navigation LinksHome > February 15, 2002 - Volume 16 - Issue 3 > Lack of control of T cell apoptosis under HAART. Influence o...
Basic Science

Lack of control of T cell apoptosis under HAART. Influence of therapy regimen in vivo and in vitro

Pinto, Luzia Maria de Oliveiraa; Lecoeur, Hervéa; Ledru, Erica; Rapp, Christopheb; Patey, Olivierc; Gougeon, Marie-Lisea

Collapse Box


Background: Increased and premature T cell apoptosis is recognized as a feature of HIV infection, and its normalization during highly active antiretroviral therapy (HAART) is thought to contribute to quantitative CD4 T cell restoration.

Design: Cross-sectional study of spontaneous, CD3- and CD95-mediated apoptosis in lymphocytes from 53 HIV-infected individuals taking HAART.

Methods: Overnight stimulation of peripheral blood mononuclear cells (PBMC) with coated anti-CD3 or anti-CD95 monoclonal antibodies or incubation overnight in medium. Apoptosis in CD4 and CD8 T cells was measured by flow cytometry. For in vitro assay of antiretroviral drugs, normal PBMC were prestimulated with anti-CD3 monoclonal antibodies and apoptosis was induced by ligation of CD95. The expression of active caspase-8 and caspase-3 was examined by flow cytometry.

Results: We report for the first time that important levels of T cell apoptosis may persist under HAART, in spite of a rise in CD4 T cells from baseline and a sustained suppression of plasmatic viral load. Spontaneous CD3- or CD95-induced apoptosis levels were inversely correlated with the in vivo number of CD4 T cells and the CD4/CD8 ratio, but not with the viral load or duration of antiretroviral therapy. Regimens including lamivudine are associated with persistent T cell apoptosis, particularly following CD95 ligation. Lamivudine was also found to stimulate in vitro CD95-induced apoptosis and caspase activation in pre-activated T lymphocytes from healthy donors.

Conclusion: The immunomodulatory effect of lamivudine may be one of the contributing factor to increased levels of T cell apoptosis under HAART. The data suggest that there is a requirement for physiological apoptosis during HAART.

© 2002 Lippincott Williams & Wilkins, Inc.


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.