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Updated: May 12, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
Mutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals
Paul Koenen1, Susanne Heinzel, Emma M Carrington
1The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria 3052, Australia.
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.
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