The thymus and central tolerance

T cell tolerance to self-components occurs largely in the thymus during ear ly differentiation and leads to death (negative selection) of T cells with overt autoreactivity. In this article we review the evidence that negative selection in mice occurs mainly in the medulla at the level of a population of semimature T cells. The role of Fas and several costimulatory molecules on negative selection and the inhibitory role of certain cytokines are dis cussed. (C) 2000 Academic Press.