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

Author

Listed:
  • Paul Koenen

    (The Walter and Eliza Hall Institute for Medical Research)

  • Susanne Heinzel

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Emma M. Carrington

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Lina Happo

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Warren S. Alexander

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Jian-Guo Zhang

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Marco J. Herold

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Clare L. Scott

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Andrew M. Lew

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Andreas Strasser

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

  • Philip D. Hodgkin

    (The Walter and Eliza Hall Institute for Medical Research
    The University of Melbourne)

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.

Suggested Citation

  • 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 & Philip D. Hodgkin, 2013. "Mutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals," Nature Communications, Nature, vol. 4(1), pages 1-10, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2719
    DOI: 10.1038/ncomms2719
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