INTERLEUKIN-12 IS A COSTIMULATORY CYTOKINE FOR LEUKEMIC CD3(+) LARGE GRANULAR LYMPHOCYTES

被引:9
作者
GENTILE, TC
LOUGHRAN, TP
机构
[1] SUNY SYRACUSE,HLTH SCI CTR,DEPT MICROBIOL & IMMUNOL,SYRACUSE,NY 13210
[2] DEPT VET AFFAIRS MED CTR,SYRACUSE,NY 13210
关键词
D O I
10.1006/cimm.1995.0018
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The activation signals leading to proliferation of leukemic CD3(+) large granular lymphocytes (LGL) are incompletely understood. In this study, the role of recombinant human interleukin-12 (rhIL-18) alone or in combination with other activation signals was studied in vitro. Anti-CD3 monoclonal antibody (MoAb) alone caused marked stimulation of peripheral blood mononuclear cells (PBMC) from three CD3(+) LGL leukemic patients, whereas rhIL-12 alone had less effect as measured in a [H-3]thymidine incorporation assay. The combination signals of anti-CD3 MoAb and rhIL-12 produced a proliferative response greater than anti-CD3 MoAb alone or rhIL-18 alone. Leukemic LGL, purified by CD8(+) affinity chromatography, showed similar proliferative responses as PBMC from LGL leukemic patients, suggesting that the observed effect was indeed due to direct stimulation of leukemic LGL. Radio-labeled IL-12 binding studies demonstrated that anti-CD3 MoAb upregulated the number of IL-12 receptors per cell on PBMC from these patients. Neutralizing antibody to rhIL-12 partially blocked the proliferative response to anti-CD3 MoAb suggesting involvement of IL-12 in the pathway of activation of leukemic LGL via stimulation of the T cell receptor (TCR) (mimicking activation by antigen). These results show that IL-12 acts as a costimulatory cytokine for proliferation of leukemic LGL activated through the TCR in vitro.(C) 1995 Academic Press, Inc.
引用
收藏
页码:158 / 161
页数:4
相关论文
共 15 条
[1]  
APRILE JA, 1991, BLOOD, V78, P1282
[2]  
BERTAGNOLLI MM, 1992, J IMMUNOL, V149, P3778
[3]  
GATELY MK, 1991, J IMMUNOL, V147, P874
[4]   IDENTIFICATION AND PURIFICATION OF NATURAL-KILLER CELL STIMULATORY FACTOR (NKSF), A CYTOKINE WITH MULTIPLE BIOLOGIC EFFECTS ON HUMAN-LYMPHOCYTES [J].
KOBAYASHI, M ;
FITZ, L ;
RYAN, M ;
HEWICK, RM ;
CLARK, SC ;
CHAN, S ;
LOUDON, R ;
SHERMAN, F ;
PERUSSIA, B ;
TRINCHIERI, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 170 (03) :827-845
[5]  
LANIER LL, 1986, J IMMUNOL, V136, P4480
[6]   LARGE ANTIGRANULOCYTES LYMPHOCYTE LEUKEMIA - REPORT OF 38 CASES AND REVIEW OF THE LITERATURE [J].
LOUGHRAN, TP ;
STARKEBAUM, G .
MEDICINE, 1987, 66 (05) :397-405
[7]  
LOUGHRAN TP, 1993, BLOOD, V82, P1
[8]  
LOUGHRAN TP, 1990, BLOOD, V75, P935
[9]  
LOUGHRAN TP, 1990, BLOOD, V69, P935
[10]   ANALYSIS OF RADIOLIGAND BINDING EXPERIMENTS - A COLLECTION OF COMPUTER-PROGRAMS FOR THE IBM-PC [J].
MCPHERSON, GA .
JOURNAL OF PHARMACOLOGICAL METHODS, 1985, 14 (03) :213-228