Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival

Immunity. 2004 Aug;21(2):289-302. doi: 10.1016/j.immuni.2004.07.016.

Abstract

Survival of naive T cells is dependent upon IL-7, which is present in vivo in limiting amounts with the result that naive T cells must compete for IL-7-mediated survival signals. It would seem imperative during T cell homeostasis that limiting IL-7 be shared by the greatest possible number of T cells. We now describe a novel regulatory mechanism that specifically suppresses IL7Ralpha transcription in response to IL-7 and other prosurvival cytokines (IL-2, IL-4, IL-6, and IL-15). Consequently, IL7R expression is reduced on T cells that have received cytokine-mediated survival signals so they do not compete with unsignaled T cells for remaining IL-7. Interestingly, cytokine-mediated suppression of IL7Ralpha transcription involves different molecular mechanisms in CD4+ and CD8+ T cells, as CD8+ T cells utilize the transcriptional repressor GFI1 while CD4+ T cells do not. We suggest that this homeostatic regulatory mechanism promotes survival of the maximum possible number of T cells for the amount of IL-7 available.

MeSH terms

  • Animals
  • Cell Survival / immunology
  • Cell Survival / physiology*
  • Gene Expression Regulation / immunology*
  • Interleukin-7 / immunology
  • Interleukin-7 / metabolism*
  • Mice
  • Receptors, Interleukin-4 / biosynthesis
  • Receptors, Interleukin-4 / genetics
  • Receptors, Interleukin-7 / biosynthesis
  • Receptors, Interleukin-7 / genetics*
  • Receptors, Interleukin-7 / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Interleukin-7
  • Receptors, Interleukin-4
  • Receptors, Interleukin-7
  • interleukin-7 receptor, alpha chain