Preferential recognition of self antigens despite normal thymic deletion of CD4+ CD25+ regulatory T cells
P Romagnoli, D Hudrisier… - The Journal of …, 2002 - journals.aai.org
P Romagnoli, D Hudrisier, JPM van Meerwijk
The Journal of Immunology, 2002•journals.aai.orgT 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 …
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 …
Abstract
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.
journals.aai.org