CORRELATION OF CALCINEURIN PHOSPHATASE-ACTIVITY AND PROGRAMMED CELL-DEATH IN MURINE T-CELL HYBRIDOMAS

被引:104
作者
FRUMAN, DA
MATHER, PE
BURAKOFF, SJ
BIERER, BE
机构
[1] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115
[2] HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115
[3] HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115
[4] HARVARD UNIV,SCH MED,DIV MED SCI,BOSTON,MA 02115
[5] HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115
关键词
D O I
10.1002/eji.1830221008
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ligation of T cell receptor/CD3 complexes induces programmed cell death, or apoptosis, in immature thymocytes and many T cell hybridomas.While it has been demonstrated that T cell receptor-mediated apoptosis requires an increase in intracellular calcium concentration. the specific calcium-dependent signalling events leading to cell death are poorly defined. We have previously shown that T cell receptor/CD3-mediated induction of apoptosis in a murine T cell hybridoma is inhibited by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Recently, it has been determined that these agents inhibit the activity of calcineurin, a calcium- and calmodulin-dependent serine/threonine phosphatase. Using an assay which measures calcineurin activity in cell lysates, we find that calcineurin-dependent dephosphorylation of a phosphopeptide substrate is potently inhibited in hybridomas treated with CsA or FK506. Drug dose-response analyses indicate that the level of cellular calcineurin activity correlates closely with the ability of these cells to undergo apoptosis. Thus, calcineurin appears to be a critical mediator of T cell receptor/CD3 signalling leading to programmed cell death in T cell hybridomas.
引用
收藏
页码:2513 / 2517
页数:5
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