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Sci. Signal., 15 November 2011
Vol. 4, Issue 199, p. ra77
[DOI: 10.1126/scisignal.2002246]

RESEARCH ARTICLES

The Long-Term Survival Potential of Mature T Lymphocytes Is Programmed During Development in the Thymus

Charles Sinclair1*, Manoj Saini1*{dagger}, Ina Schim van der Loeff1, Shimon Sakaguchi2, and Benedict Seddon1{ddagger}

1 Division of Immune Cell Biology, Medical Research Council, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
2 Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

* These authors contributed equally to this work.

{dagger} Present address: Academic Department of Rheumatology, Center for Molecular and Cellular Biology of Inflammation, Kings College London, London SE1 1UL, UK.

Abstract: The homeostatic maintenance of normal numbers of mature T lymphocytes in the immune system depends on signaling from the T cell antigen receptor (TCR) and the interleukin-7 receptor (IL-7R); however, it is unclear whether there is crosstalk between these two receptors. Here, we have identified a central role for TCR signaling during the development of T lymphocytes in the thymus in the determination of IL-7 function in mature T lymphocytes. We showed that Il7r expression in mature T cells was modulated by developmental TCR-dependent signals elicited during the process of positive selection in the thymus and that this mechanism was common to both CD4+ and CD8+ T cells. Control of Il7r expression by the TCR was limited to thymocytes because neither the abundance nor the function of IL-7Rα was affected by TCR signaling in peripheral T cells. Finally, we showed that thymocytes without optimal IL-7Rα abundance failed to form part of the pool of mature T lymphocytes that patrol the periphery of normal hosts, highlighting the importance of this mechanism in shaping the repertoire of lymphocytes that make up this population.

{ddagger} To whom correspondence should be addressed. E-mail: bseddon{at}nimr.mrc.ac.uk

Citation: C. Sinclair, M. Saini, I. Schim van der Loeff, S. Sakaguchi, B. Seddon, The Long-Term Survival Potential of Mature T Lymphocytes Is Programmed During Development in the Thymus. Sci. Signal. 4, ra77 (2011).

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