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
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
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.