Spontaneous programmed cell death of peripheral blood mononuclear cells from HIV-infected persons is decreased with interleukin-15

Interleukin 15 (IL-15) is an important regulatory cytokine in cellular immu nity. In vitro replacement of IL-15 has been shown to enhance immunity in H uman immunodeficiency virus type 1 (HIV-1) infected lymphocytes. We evaluat ed the effect of IL-15 on the survival of peripheral blood mononuclear cell s of HIV patients by examining in vitro lymphocyte apoptosis, and correlate d the process with Bcl-2 and Fas gene regulation. Peripheral blood mononucl ear cells (PBMC) from 21 HIV-infected adults and 24 HIV-seronegative health y individuals were isolated and cultured to determine the effect of escalat ing doses of IL-15 (0, 1, 10, 100, 1000 ng/mL) on apoptosis. Lymphocyte pro liferation assay with (H-3) TdR was measured and Bcl-2 and Fas gene regulat ion was observed. The results mere as follows: 1) IL-15 reduced culture ind uced lymphocyte apoptosis in HIV patients in a dose dependent manner, and r eached a plateau level at a concentration of 100 ng/ml; 2) IL-15 significan tly reduced the level of apoptosis after 3 days (14%) and 5 days (15%) of c ulture in HIV patients, while no difference was observed in HIV (-) donors; 3) The percentage of viable cells among the total number of lymphocytes wa s significantly enhanced by 25% in HIV patients with IL-15; 4) Bcl-2 expres sion was decreased in HIV patients (53.9+/-12.3%) compared to HIV (-) donor s (93.0+/-3.7%), and IL-15 increased Bcl-2 expression by 21.2+/-5.2% in HIV patients, 5) Fas expression was increased in HIV patients (70.2+/-4.6%) co mpared to HIV ( -) donors (32.4+/-4.3%), and IL-15 increased Fas expression by 8.4+/-1.2% in HIV (-) donors. Our findings indicate that IL-15 may infl uence immunologic abnormalities in HN infection, particularly its ability t o prevent apoptosis of lymphocytes by suppressing the down-modulation of Bc l-2. This may provide an experimental basis for IL-15 immunotherapy.