Maintenance of tolerance to self antigens is presumed to reflect a combination of central and
peripheral tolerance. For T cells, central tolerance occurs during early T cell development in
the thymus and causes cells with strong reactivity to self antigens to be destroyed in situ
(negative selection). Here, we summarize evidence that negative selection can occur in the
thymic medulla and affects a population of semimature HSA+ T cells. The influence of
costimulatory molecules, Fas and cytokines on negative selection is discussed.