A new mechanism of thymic selection

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).

This would suggest that specificity for self-peptides directs the selection of CD4+CD25+ regulatory thymocytes by a process that ...