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¹ Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, and ² Department of Pathology, New York University School of Medicine, New York, NY 10016

CORRESPONDENCE Juan J. Lafaille: juan.lafaille{at}med.nyu.edu OR Shiqian Shen: shiqian.shen{at}gmail.com

Numerous studies have highlighted the importance of high-affinity interactions between T cell receptors (TCRs) and their ligands in the selection of Foxp3⁺ regulatory T cells (T reg cells). To determine the role of the TCR in directing T cells into the Foxp3⁺ lineage, we generated transgenic (Tg) mice expressing TCRs from Foxp3⁺ cells. Initial analyses of the TCR Tg mice crossed with RAG-deficient mice showed that the percentage of Foxp3⁺ cells was very low. However, intrathymic injection and bone marrow chimera experiments showed a saturable increase of the Foxp3⁺ population when T reg TCR Tg cells were present in low numbers. Furthermore, when analyzing whole thymi of T reg TCR Tg RAG-deficient mice, we found significantly more Foxp3⁺ cells than in conventional T cell TCR Tg mice. Our results indicate that although the TCR has an instructive role in determining Foxp3 expression, selection of Foxp3⁺ individual clones in the thymus is limited by a very small niche.

S. Shen's present address is Dept. of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114.

Abbreviations used: cDNA, complementary DNA; DN, double negative; DP, double positive; GITR, glucocorticoid-induced tumor necrosis factor receptor; MBP, myelin basic protein; T conv, conventional T cell; T reg cell, regulatory T cell; Tg, transgenic.

© 2009 Leung et al.
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