SIGNALING REQUIREMENTS FOR THE EXPRESSION OF THE TRANSACTIVATING FACTOR NF-AT IN HUMAN LYMPHOCYTES-T

被引:30
作者
HIVROZBURGAUD, C [1 ]
CLIPSTONE, NA [1 ]
CANTRELL, DA [1 ]
机构
[1] IMPERIAL CANC RES FUND,LYMPHOCYTE ACTIVAT LAB,POB 123,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND
关键词
D O I
10.1002/eji.1830211124
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A protein called nuclear factor of activated T cells (NF-AT) binds to DNA sequences within the enhancer region of the interleukin 2 (IL2) gene and appears necessary for both the inducibility and T cell specificity of IL2 expression. IL2 production is regulated by multiple signals including those generated via activation of the T cell antigen receptor complex (TcR/CD3), CD2 antigen, protein kinase C (PKC) or elevation of intracellular free calcium concentration ([Ca2+]i). We have, therefore, explored the role of these different stimuli in regulating the nuclear expression of NF-AT in human peripheral blood-derived lymphocytes. Results presented herein indicate that maximal expression of NF-AT in T cells requires at least two signals: PKC activation and TcR/CD3 or CD2 triggering, [Ca2+]i increases and TcR/CD3 or CD2 triggering. Data are presented that indicate that either the [Ca2+]i or PKC signal generated via the TcR/CD3 complex would not alone induce NF-AT expression, and that the TcR/CD3 complex probably regulates NF-AT expression because of its ability to regulate multiple intracellular signals in T cells, and not via any single biochemical event. The combination of CD2 mAb GT2/OKT11 used in the present study to trigger the CD2 antigen is able to act in synergy with phorbol 12,13-dibutyrate or inomycin to induce NF-AT expression. However, these CD2 mAb do not elevate [Ca2+]i or activate PKC, suggesting that signals other than [Ca2+]i or PKC can regulate NF-AT expression in peripheral blood-derived T cells.
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页码:2811 / 2819
页数:9
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