title: The thymic niche does not limit development of the naturally diverse population of mouse regulatory T lymphocytes.
abstract: Thymus-derived CD4(+)Foxp3(+) regulatory T lymphocytes (Tregs) play a central role in the suppression of immune responses to self-antigens and thus avoid autoimmune disorders. It remains unclear if the specialized thymic niche controls the number of differentiating Tregs. We investigated development of murine Tregs from precursors expressing the naturally very large repertoire of TCRs. By analyzing their developmental kinetics, we observed that differentiating Tregs dwell in the thymus ∼1 d longer than their conventional T cell counterparts. By generating hematopoietic chimeras with very low proportions of trackable precursors, we could follow individual waves of developing T cells in the thymus. We observed strongly increased proportions of Tregs at the end of the waves, confirming that these cells are the last to leave the thymus. To assess whether the thymic niche limits Treg development, we generated hematopoietic chimeras in which very few T cell precursors could develop. The substantial increase in the proportion of Tregs we found in these mice suggested a limiting role of the thymic niche; however, this increase was accounted for entirely by the prolonged thymic dwell time of Tregs. We conclude that, when precursors express a naturally diverse TCR repertoire, the thymic niche does not limit differentiation of Tregs.
authors.affiliation: INSERM U1043, Toulouse, F-31300, France. Paola.Romagnoli@inserm.fr
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnoli
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.forename: Genevieve
authors.initials: G
authors.lastname: Enault
authors.forename: Rita
authors.initials: R
authors.lastname: Vicente
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.forename: Joost P M
authors.initials: JP
authors.lastname: van Meerwijk
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005456:Fluorescent Dyes; D055879:Gene Knock-In Techniques; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins