The long-term survival potential of mature T lymphocytes is programmed during development in the thymus

Sci Signal. 2011 Nov 15;4(199):ra77. doi: 10.1126/scisignal.2002246.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Survival
  • Gene Expression Regulation / immunology
  • Mice
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-7 / biosynthesis
  • Receptors, Interleukin-7 / immunology
  • Signal Transduction / immunology*
  • Thymocytes / cytology
  • Thymocytes / immunology*
  • Thymocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-7