Thymic selection and lineage commitment of CD4(+)Foxp3(+) regulatory T lymphocytes.

Regulatory T lymphocytes play a central role in the control of a variety of immune-responses. Their absence in humans and in experimental animal models leads to severe autoimmune and inflammatory disorders. Consistent with their major role in prevention of autoimmune pathology, their repertoire is enriched in autospecific cells. Probably the majority of regulatory T cells develop in the thymus. How T cell-precursors choose between the conventional versus regulatory T cell lineages remains an unanswered question. More is known about selection of regulatory T cell precursors. Positive selection of these cells is favored by high affinity interactions with MHC class II/peptide ligands expressed by thymic epithelial or dendritic cells. They are also known to be relatively resistant to negative selection. These two parameters allow for the generation of the autoreactive regulatory T cell repertoire, and clearly distinguish selection-criteria of conventional versus regulatory T cell-precursors. It will now be important to elucidate the molecular mechanisms involved in the intrathymic choice of the regulatory T cell-lineage.