The GTPase Rac-1 controls cell fate in the thymus by diverting thymocytes from positive to negative selection

The positive selection of CD4 or CD8 single-positive mature peripheral T ly mphocytes and the deletion of self-reactive cells are crucial for central t olerance in the peripheral immune system. Previously, the guanine nucleotid e binding protein Rac-1 has been shown to control pre-T cell development. T he present report now describes the actions of Rac-1 in thymocyte selection . The study reveals that this molecule has the striking and unique ability to efficiently divert cells from positive selection into a pathway of negat ive selection and deletion. The ability of Rac-1 to switch thymocytes from a destiny of positive to negative selection identifies this molecule as a c ritical regulator of the developmental processes in T cells that are essent ial for immune homeostasis.