title: The long-term survival potential of mature T lymphocytes is programmed during development in the thymus.
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.
authors.affiliation: Division of Immune Cell Biology, Medical Research Council, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Sinclair
authors.forename: Manoj
authors.initials: M
authors.lastname: Saini
authors.forename: Ina
authors.initials: I
authors.lastname: Schim van der Loeff
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Benedict
authors.initials: B
authors.lastname: Seddon
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7