Mutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals

Paul Koenen, Susanne Heinzel, Emma M. Carrington, Lina Happo, Warren S. Alexander, Jian-Guo Zhang, Marco J. Herold, Clare L. Scott, Andrew M. Lew, Andreas Strasser and Philip D. Hodgkin ()
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Paul Koenen: The Walter and Eliza Hall Institute for Medical Research
Susanne Heinzel: The Walter and Eliza Hall Institute for Medical Research
Emma M. Carrington: The Walter and Eliza Hall Institute for Medical Research
Lina Happo: The Walter and Eliza Hall Institute for Medical Research
Warren S. Alexander: The Walter and Eliza Hall Institute for Medical Research
Jian-Guo Zhang: The Walter and Eliza Hall Institute for Medical Research
Marco J. Herold: The Walter and Eliza Hall Institute for Medical Research
Clare L. Scott: The Walter and Eliza Hall Institute for Medical Research
Andrew M. Lew: The Walter and Eliza Hall Institute for Medical Research
Andreas Strasser: The Walter and Eliza Hall Institute for Medical Research
Philip D. Hodgkin: The Walter and Eliza Hall Institute for Medical Research

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: 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.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2719

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DOI: 10.1038/ncomms2719

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