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

被引:8
作者
Chang, KH [1 ]
Kim, JM [1 ]
Kim, HY [1 ]
Song, YG [1 ]
Choi, YH [1 ]
Park, YS [1 ]
Cho, JH [1 ]
Hong, SK [1 ]
机构
[1] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea
关键词
interleukin; 15; lymphocyte; apoptosis; Human Immunodeficiency Virus;
D O I
10.3349/ymj.2000.41.1.112
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (H-3) TdR was measured and Bcl-2 and Fas gene regulation was observed. The results mere 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 HN 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.
引用
收藏
页码:112 / 118
页数:7
相关论文
共 32 条
[1]   Interleukin-2 receptor common gamma-chain signaling cytokines regulate activated T cell apoptosis in response to growth factor withdrawal: Selective induction of anti-apoptotic (bcl-2, bcl-x(L)) but not pro-apoptotic (bax, bcl-x(S)) gene expression [J].
Akbar, AN ;
Borthwick, NJ ;
Wickremasinghe, RG ;
Panayiotidis, P ;
Pilling, D ;
Bofill, M ;
Krajewski, S ;
Reed, JC ;
Salmon, M .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (02) :294-299
[2]  
AMEISEN JC, 1991, IMMUNOL TODAY, V12, P102
[3]   CROSS-LINKING CD4 BY HUMAN IMMUNODEFICIENCY VIRUS-GP120 PRIMES T-CELLS FOR ACTIVATION-INDUCED APOPTOSIS [J].
BANDA, NK ;
BERNIER, J ;
KURAHARA, DK ;
KURRLE, R ;
HAIGWOOD, N ;
SEKALY, RP ;
FINKEL, TH .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (04) :1099-1106
[4]  
BOFILL M, 1995, AM J PATHOL, V146, P1542
[5]  
BROOME HE, 1995, J IMMUNOL, V155, P2311
[6]   TYPE-1 TYPE-2 CYTOKINE MODULATION OF T-CELL PROGRAMMED CELL-DEATH AS A MODEL FOR HUMAN-IMMUNODEFICIENCY-VIRUS PATHOGENESIS [J].
CLERICI, M ;
SARIN, A ;
COFFMAN, RL ;
WYNN, TA ;
BLATT, SP ;
HENDRIX, CW ;
WOLF, SF ;
SHEARER, GM ;
HENKART, PA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) :11811-11815
[7]  
COHEN JJ, 1993, IMMUNOL TODAY, V14, P126, DOI 10.1016/0167-5699(93)90214-6
[8]   APOPTOSIS OCCURS PREDOMINANTLY IN BYSTANDER CELLS AND NOT IN PRODUCTIVELY INFECTED-CELLS OF HIV-INFECTED AND SIV-INFECTED LYMPH-NODES [J].
FINKEL, TH ;
TUDORWILLIAMS, G ;
BANDA, NK ;
COTTON, MF ;
CURIEL, T ;
MONKS, C ;
BABA, TW ;
RUPRECHT, RM ;
KUPFER, A .
NATURE MEDICINE, 1995, 1 (02) :129-134
[9]  
GOUGEON ML, 1991, CR ACAD SCI III-VIE, V312, P529
[10]   PROGRAMMED CELL-DEATH IN AIDS-RELATED HIV AND SIV INFECTIONS [J].
GOUGEON, ML ;
GARCIA, S ;
HEENEY, J ;
TSCHOPP, R ;
LECOEUR, H ;
GUETARD, D ;
RAME, V ;
DAUGUET, C ;
MONTAGNIER, L .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1993, 9 (06) :553-563