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 counts in HIV+ patients. We have previously reported that PBMC from HIV-infected patients undergo marked spontaneous apoptosis in vitro. In this study, we examined the effect of IL-2 added in vitro upon culture-induced apoptosis in PBMC from 80 HIV-infected patients by flow cytometry. IL-2 at concentrations of > or = 10 U/ml significantly reduced spontaneous apoptosis in CD3+ T lymphocytes in patients but not in healthy volunteers. Interestingly, we observed that Bcl-2 expression in patient lymphocytes decreased rapidly upon in vitro culture while that in cells of healthy volunteers was relatively unaffected. The most significant decrease in Bcl-2 expression was noted in the apoptotic cell population. The IL-2-mediated reduction in lymphocyte apoptosis was found to be associated with the blocking of this culture-induced down-modulation of Bcl-2 expression. IL-2 did not induce significant expansion of lymphocytes during the culture period nor did it affect Fas Ag expression in patient cells, which were already expressing Fas maximally. These findings strongly suggest that IL-2 mediates its apoptosis-blocking effects via suppressing down-modulation of Bcl-2. Our findings also provide an experimental basis for the ongoing therapies utilizing this cytokine for slowing HIV disease progression.
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030, USA.
Y
Y
Adachi
N
N
Oyaizu
S
S
Than
T W
TW
McCloskey
S
S
Pahwa
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003864:Depression, Chemical; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor