TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes.
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.
Leung
Monica W L
MW
Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Shen
Shiqian
S
Lafaille
Juan J
JJ
D000818:Animals; D015704:CD4 Antigens / Q000502:physiology; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell