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. 1995 Mar 14;92(6):2375–2378. doi: 10.1073/pnas.92.6.2375

Negative transcriptional regulation in anergic T cells.

J C Becker 1, T Brabletz 1, T Kirchner 1, C T Conrad 1, E B Bröcker 1, R A Reisfeld 1
PMCID: PMC42486  PMID: 7892274

Abstract

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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