The thymus prevents autoimmunity by inducing apoptosis of the T cells that express autoreactive receptors to self peptides. But this mechanism alone is insufficient and CD4+CD25+ regulatory T cells are selected in the thymus to control autoreactive thymic escapees. In the April Nature Immunology, researchers from The Wistar Institute, Philadelphia, describe a novel mechanism of thymic selection that is involved in the generation of CD4+CD25+ regulatory T cells.

Using a murine model, Jordan et al found that a single self peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR) to undergo selection to become CD4+CD25+ regulatory T cells. Selection of CD4+CD25+ thymocytes requires a TCR with high affinity for the peptide. Thymocytes that bear TCRs with low affinity do not undergo selection into this pathway (Nat Immun 2001, 2:301-306).

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