NEGATIVE TRANSCRIPTIONAL REGULATION IN ANERGIC T-CELLS

被引:62
作者
BECKER, JC
BRABLETZ, T
KIRCHNER, T
CONRAD, CT
BROCKER, EB
REISFELD, RA
机构
[1] UNIV ERLANGEN NURNBERG, INST PATHOL, D-91054 ERLANGEN, GERMANY
[2] UNIV WURZBURG, DEPT DERMATOL, D-97080 WURZBURG, GERMANY
关键词
D O I
10.1073/pnas.92.6.2375
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Anergy is a mechanism of T-lymphocyte tolerance induced by antigen-receptor stimulation in the absence of costimulation, whereby T cells exhibit a defect in antigen-induced transcription of the interleukin 2 (IL-2) gene. Here we present evidence for a mechanism of negative IL-2 gene regulation in anergic T cells, High amounts of binding activity to the negative regulatory element A (NRE-A) of the IL-2 promotor were detected in nuclear extracts from human T cells shortly after induction of anergy. Rapid induction of this nuclear complex is blocked by cyclosporin A and is found to be independent of protein synthesis. Plasmid DNAs, containing either the human phorbol 12-myristate 13-acetate-responsive element (PRE) or both NRE-A and PRE, were used as template for in vitro transcription assays in the presence of T-cell nuclear extracts. Under these conditions nuclear extracts from both anergic and rested T-cell clones, after crosslinking of CD3 and CD28, induced transcription of plasmids containing only PRE. However, when plasmids containing NRE-A and PRE were used, transcription was only induced by nuclear extracts from rested but not anergic T cells. These findings suggest the functional relevance of transcriptional repression of the IL-2 gene in anergic T cells.
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页码:2375 / 2378
页数:4
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