Thymic and intestinal intraepithelial T lymphocyte development are each regulated by the γc-dependent cytokines IL-2, IL-7, and IL-15

Brian O. Porter, Thomas R. Malek

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Both thymic and extrathymic T lineage development are characterized by cytokine-dependent regulation of complex proliferative, differentiative, and anti-apoptotic processes. The role of the γc-dependent cytokines in this program has been interpreted as limited to the activity of IL-7. However, through the analysis of double knock-out mice, which lack signaling through the IL-7R and other γc-dependent cytokines, we revealed a role for IL-15 in the production of early thymic pro-T cells. Although IL-2 does not function in the production of thymocytes, thymic restoration of IL-2R expression prevented fatal autoimmunity associated with IL-2- or IL-2R-deficient mice, suggesting that IL-2R functions non-redundantly at the level of the thymus to regulate self-reactivity. Moreover, IL-2, IL-7, and IL-15 also extend their developmental effects beyond the thymus to other sites of T lymphocyte production, including the gut. Here, their redundant and non-redundant activities are directly correlated to the development of phenotypically diverse subsets of intestinal intraepithelial lymphocytes. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)465-474
Number of pages10
JournalSeminars in Immunology
Volume12
Issue number5
DOIs
StatePublished - Jan 1 2000

Keywords

  • Development
  • IL-15
  • IL-2
  • IL-7
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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