Mutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals
Journal Title
NATURE COMMUNICATIONS
Publication Type
Journal Article
Abstract
Two major processes govern T cell proliferation and survival: interleukin-7-mediated homeostasis and antigen-induced selection. How cells transit between the two states is unknown. Here we show that T cell receptor ligation actively inhibits homeostatic survival signals while initiating a new, dominant survival programme. This switch is mediated by a change in the expression of pro-and anti-apoptosis proteins through the downregulation of Bcl-2 and the induction of Bim, A1 and Bcl-xL. Calcineurin inhibitors prevent the initiation of the new survival programme, while permitting the dominant repression of Bcl-2. Thus, in the presence of these drugs the response to antigen receptor ligation is cell death. Our results identify a molecular switch that can serve as an attractive target for inducing antigen-specific tolerance in treating autoimmune disease patients and transplant recipients.
Publisher
NATURE PUBLISHING GROUP
Keywords
PROTEIN-KINASE KINASE; IN-VIVO; CYCLOSPORINE-A; DEFICIENT MICE; IMMUNE-SYSTEM; BCL-2; HOMEOSTASIS; DEATH; BIM; PROLIFERATION
Research Division(s)
Molecular Genetics Of Cancer; Cancer And Haematology; Immunology; Stem Cells And Cancer
Terms of Use/Rights Notice
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Creation Date: 2013-04-01 12:00:00
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