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Molecular Signature of Recent Thymic Selection Events on Effector and Regulatory CD4⁺ T Lymphocytes¹

Paola Romagnoli^2,*, Denis Hudrisier^*, and Joost P. M. van Meerwijk^*,,

^* Institut National de la Santé et de la Recherche Médicale, Unité 563, Centre de Physiopathologie Toulouse Purpan, Toulouse, France; University Toulouse III, Toulouse, France; and Institut Universitaire de France, Paris, France

Natural CD4⁺CD25⁺ regulatory T lymphocytes (T_reg) are key protagonists in the induction and maintenance of peripheral T cell tolerance. Their thymic origin and biased repertoire continue to raise important questions about the signals that mediate their development. We validated analysis of MHC class II capture by developing thymocytes from thymic stroma as a tool to study quantitative and qualitative aspects of the cellular interactions involved in thymic T cell development and used it to analyze T_reg differentiation in wild-type mice. Our data indicate that APCs of bone marrow origin, but, surprisingly and importantly, not thymic epithelial cells, induce significant negative selection among the very autoreactive T_reg precursors. This fundamental difference between thymic development of regulatory and effector T lymphocytes leads to the development of a T_reg repertoire enriched in cells specific for a selected subpopulation of self-Ags, i.e., those specifically expressed by thymic epithelial cells.

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IN THIS ISSUE

The JI 2005 175: 5565-5566. [Full Text]  

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