Preferential recognition of self antigens despite normal thymic deletion of CD4(+)CD25(+) regulatory T cells.
T cell tolerance to self Ags is in part established in the thymus by induction of apoptosis or anergy of potentially autoreactive thymocytes. Some autospecific T cells nevertheless migrate to peripheral lymphoid organs but are kept under control by the recently identified CD4(+)CD25(+) regulatory T cell subset. Because these cells inhibit autoimmunity more efficiently than useful non-self Ag-specific immune responses, they are probably autospecific, posing important questions as to how they develop in the thymus. In this study we show that significantly more peripheral CD4(+)CD25(+) regulatory T cells recognize self than non-self Ags. However, we also show for a large panel of endogenous superantigens as well as for self peptide/MHC complexes that autospecific CD4(+)CD25(+) thymocyte precursors are normally deleted during ontogeny. Combined, our data firmly establish that the repertoire of regulatory T cells is specifically enriched in autospecific cells despite the fact that their precursors are normally susceptible to thymic deletion.
Romagnoli
Paola
P
Institut National de la Santé et de la Recherche Médicale, Claude de Preval Institute, Purpan Hospital, Toulouse, France. Paola.Romagnoli@toulouse.inserm.fr
Hudrisier
Denis
D
van Meerwijk
Joost P M
JP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D017637:Clonal Deletion; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013234:Stem Cells / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
D001324:Autoantigens; D015375:Receptors, Interleukin-2; D018089:Superantigens