PROGRAMMED CELL-DEATH IN PERIPHERAL LYMPHOCYTES FROM HIV-INFECTED PERSONS - INCREASED SUSCEPTIBILITY TO APOPTOSIS OF CD4 AND CD8 T-CELLS CORRELATES WITH LYMPHOCYTE-ACTIVATION AND WITH DISEASE PROGRESSION

Citation
Ml. Gougeon et al., PROGRAMMED CELL-DEATH IN PERIPHERAL LYMPHOCYTES FROM HIV-INFECTED PERSONS - INCREASED SUSCEPTIBILITY TO APOPTOSIS OF CD4 AND CD8 T-CELLS CORRELATES WITH LYMPHOCYTE-ACTIVATION AND WITH DISEASE PROGRESSION, The Journal of immunology, 156(9), 1996, pp. 3509-3520
Citations number
58
Categorie Soggetti
Immunology
Journal title
The Journal of immunology
ISSN journal
00221767 → ACNP
Volume
156
Issue
9
Year of publication
1996
Pages
3509 - 3520
Database
ISI
SICI code
0022-1767(1996)156:9<3509:PCIPLF>2.0.ZU;2-0
Abstract
We analyzed the potential causes of the increased susceptibility to ap optosis of peripheral lymphocytes from a large cohort of HIV-infected persons that we followed during a 3-yr period. By using quantitative c ytofluorometric methods, we demonstrate that all lymphocyte population s were contributing proportionally to the apoptopic population in both groups of donors, but the percentage of T and B cells involved in thi s cell death process was significantly increased in HIV-infected perso ns. To study the relationship between the increased apoptosis in HIV i nfection and the activation state of the immune system, we analyzed ce ll surface expression of activation markers on apoptotic and nonapopto tic cells. We found that in the chronic phase of HIV infection, 50 to 60% of the apoptotic cells exhibited an activated phenotype (they were HLA-DR(+), CD38(+), CD45RO(+), and Fas(+)), and interestingly, the CD 45RO(+) subset appeared to be more prone to apoptosis in HIV-positive persons. This study also indicates that the activated phenotype found on apoptotic cells was not a distinctive feature of patients' lymphocy tes since it was in similar proportion in apoptotic cells from control lymphocytes. However, a significant correlation was found between the intensity of anti-CD3-induced apoptosis in both CD4 and CD8 T cells f rom HIV-infected persons and their in vivo expression of CD45RO and HL A-DR molecules. Finally, a significant correlation was found between t he intensity of spontaneous or anti-CD3-induced apoptosis in total lym phocytes and disease progression; this was confirmed when the CD4 and CD8 T cell subsets were analyzed separately. Altogether these observat ions indicate that the increased susceptibility to apoptosis of periph eral T cells from HIV-infected persons correlates with disease progres sion and support the hypothesis that the chronic activation of the imm une system occurring throughout HIV infection is the primary mechanism responsible for this cell deletion process.