IL-2 RESCUES IN-VITRO LYMPHOCYTE APOPTOSIS IN PATIENTS WITH HIV-INFECTION - CORRELATION WITH ITS ABILITY TO BLOCK CULTURE-INDUCED DOWN-MODULATION OF BCL-2

IL-2 administration in vivo has been shown to increase CD4(+) T cell c ounts in HIV+ patients. We have previously reported that PBMC from HIV -infected patients undergo marked spontaneous apoptosis in vitro. In t his study, we examined the effect of IL-2 added in vitro upon culture- induced apoptosis in PBMC from 80 HIV-infected patients by flow cytome try, IL-2 at concentrations of greater than or equal to 10 U/ml signif icantly reduced spontaneous apoptosis in CD3+ T lymphocytes in patient s but not in healthy volunteers, Interestingly, we observed that Bcl-2 expression inpatient lymphocytes decreased rapidly upon in vitro cult ure while that in cells of healthy volunteers was relatively unaffecte d. The most significant decrease in Bcl-2 expression was noted in the apoptotic cell population. The IL-2-mediated reduction in lymphocyte a poptosis was found to be associated with the blocking of this culture- induced down-modulation of Bcl-2 expression. IL-2 did not induce signi ficant expansion of lymphocytes during the culture period nor did it a ffect Fas Ag expression in patient cells, which were already expressin g Fas maximally. These findings strongly suggest that IL-2 mediates if s apoptosis-blocking effects via suppressing down-modulation of Bcl-2. Our findings also provide an experimental basis for the ongoing thera pies utilizing this cytokine for slowing HIV disease progression.