Mutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals
- Author(s)
- Koenen, P; Heinzel, S; Carrington, EM; Happo, L; Alexander, WS; Zhang, JG; Herold, MJ; Scott, CL; Lew, AM; Strasser, A; Hodgkin, PD;
- 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
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644093/
- Publisher's Version
- https://doi.org/10.1038/ncomms2719
- Terms of Use/Rights Notice
- © 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Creation Date: 2013-04-01 12:00:00