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

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.

authors

  • Koenen, Paul
  • Heinzel, Susanne
  • Carrington, Emma M
  • Happo, Lina
  • Alexander, Warren S
  • Zhang, Jian-Guo
  • Herold, Marco J
  • Scott, Clare L
  • Lew, Andrew M
  • Strasser, Andreas
  • Hodgkin, Philip D

publication date

  • 2013