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

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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. © 2013 Macmillan Publishers Limited. All rights reserved.

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Koenen, P., Heinzel, S., Carrington, E. M., Happo, L., Alexander, W. S., Zhang, J. G., … Hodgkin, P. D. (2013). Mutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals. Nature Communications, 4. https://doi.org/10.1038/ncomms2719

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