| First Author | Daniely D | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 12 | Pages | 6865-73 |
| PubMed ID | 20483761 | Mgi Jnum | J:161141 |
| Mgi Id | MGI:4457429 | Doi | 10.4049/jimmunol.0903609 |
| Citation | Daniely D, et al. (2010) Diversity of TCRs on natural Foxp3+ T cells in mice lacking Aire expression. J Immunol 184(12):6865-73 |
| abstractText | 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+ TCRminiFoxp3GFP 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. |
