Diversity of TCRs on natural Foxp3+ T cells in mice lacking Aire expression

Danielle Daniely, Joanna Kern, Anna Cebula, Leszek Ignatowicz

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Medullary thymic epithelial cells expressing the Aire gene play a critical role in the induction of tolerance to tissue-specific Ags (TSAs). It was postulated that recognition of Aire-controlled TSAs by immature thymocytes results in the selection of natural CD4+Foxp3+ regulatory T cells (Tregs) and enriches this repertoire in self-reactive receptors, contributing to its vast diversity. In this study, we compared the TCRs on individual Tregs in Aire+ and Aire- mice expressing a miniature TCR repertoire (TCRmini) along with GFP driven by the Foxp3 promoter (Foxp3GFP). The Treg TCR repertoires in Aire+ and Aire- TCRminiFoxp3GFP mice were similar and more diverse than their repertoires on CD4+ Foxp3- thymocytes. Further, TCRs found on potentially self-reactive T cells, with an activated phenotype (CD4+Foxp3-CD62Llow) in Aire- TCRminiFoxp3GFP mice, appear distinct from TCRs found on Tregs in Aire+ TCRminiFoxp3 GFP mice. Lastly, we found no evidence that TSAs presented by medullary thymic epithelial cells in Aire+TCRmini mice are often recognized as agonists by Treg-derived TCR hybridomas or CD4 +CD25+ thymocytes, containing both natural Tregs and precursors. Thus, positive selection and self-reactivity of the global Treg repertoire are not controlled by Aire-dependent TSAs.

Original languageEnglish (US)
Pages (from-to)6865-6873
Number of pages9
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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