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

Original Article

Kyung Hee Chang, June Myung Kim, Hyo Youl Kim, Young Goo Song, Young Hwa Choi, Yoon Soo Park, Jung Ho Cho and Sung Kwan Hong

- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Address reprint requests to Dr. J. M. Kim, Department of Internal Medicine, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul 120-752, Korea. Tel: 82-2-361-5431, Fax: 82-2-393-6884,

Received October 30, 1999; Accepted December 07, 1999.

Abstract

Interleukin 15 (IL-15) is an important regulatory cytokine in cellular immunity. In vitro replacement of IL-15 has been shown to enhance immunity in Human immunodeficiency virus type 1 (HIV-1) infected lymphocytes. We evaluated the effect of IL-15 on the survival of peripheral blood mononuclear cells of HIV patients by examining in vitro lymphocyte apoptosis, and correlated the process with Bcl-2 and Fas gene regulation. Peripheral blood mononuclear cells (PBMC) from 21 HIV-infected adults and 24 HIV-seronegative healthy individuals were isolated and cultured to determine the effect of escalating doses of IL-15 (0, 1, 10, 100, 1000 ng/mL) on apoptosis. Lymphocyte proliferation assay with (3H) TdR was measured and Bcl-2 and Fas gene regulation was observed. The results were as follows: 1) IL-15 reduced culture induced lymphocyte apoptosis in HIV patients in a dose dependent manner, and reached a plateau level at a concentration of 100 ng/ml; 2) IL-15 significantly reduced the level of apoptosis after 3 days (14%) and 5 days (15%) of culture in HIV patients, while no difference was observed in HIV (-) donors; 3) The percentage of viable cells among the total number of lymphocytes was significantly enhanced by 25% in HIV patients with IL-15; 4) Bcl-2 expression was decreased in HIV patients (53.9 ± 12.3%) compared to HIV (-) donors (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%) compared 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 influence immunologic abnormalities in HIV infection, particularly its ability to prevent apoptosis of lymphocytes by suppressing the down-modulation of Bcl-2. This may provide an experimental basis for IL-15 immunotherapy.

Keywords

Interleukin 15; lymphocyte; apoptosis; Human Immunodeficiency Virus