Selective availability of IL-2 is a major determinant controlling the production of CD4+CD25+Foxp3+ T regulatory cells

Aixin Yu, Thomas R. Malek

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The development and maintenance of T regulatory (Treg) cells critically depend on IL-2. This requirement for IL-2 might be due to specificity associated with IL-2R signal transduction or because IL-2 was uniquely present in the niche in which Treg cells reside. To address this issue, we examined the capacity of IL-7R-dependent signaling to support Treg cell production and prevent autoimmunity in IL-2Rβ-/- mice. Expression of transgenic wild-type IL-7R or a chimeric receptor that consisted of the extracytoplasmic domain of the IL-7R α-chain and the cytoplasmic domain of IL-2R β-chain in IL-2Rβ-/- mice did not prevent autoimmunity. Importantly, expression of a chimeric receptor that consisted of the extracytoplasmic domain of the IL-2R β-chain and the cytoplasmic domain of IL-7R α-chain in IL-2Rβ-/- mice led to Treg cells production in the thymus and periphery and prevented autoimmunity. Signaling through the IL-2R or chimeric IL-2Rβ/IL-7Rα in vivo or the culture of thymocytes from IL-2Rβ-/- mice with IL-7 led to up-regulation of Foxp3 and CD25 on Treg cells. These findings indicate that IL-7R signal transduction is competent to promote Treg cell production, but this signaling requires triggering through IL-2 by binding to the extracytoplasmic portion of the IL-2R via this chimeric receptor. Thus, a major factor controlling the nonredundant activity of the IL-2R is selective compartmentalization of IL-2-producing cells with Treg cells in vivo.

Original languageEnglish (US)
Pages (from-to)5115-5121
Number of pages7
JournalJournal of Immunology
Volume177
Issue number8
DOIs
StatePublished - Oct 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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