Acquisition of self-tolerance in T cells is achieved by different mechanisms, operating both inside and outside the thymus.

During the past 3 years, considerable progress has been generated in understanding the mechanisms by which developing T cells acquire tolerance for self-antigens. Clonal deletion of T cells with self-reactive receptors for certain antigens expressed in the thymus was the first process to be identified as a major mechanism for generating tolerance in thymocytes. When this process fails, nondeletional mechanisms for acquisition of tolerance to self-antigens are employed. If the molecular mechanisms underlying these events are to be understood, it is crucial to identify to which extent these alternate forms of tolerance induction operate at different stages of T cells development. This article reviews where and how the tolerant state is achieved at different stages of T cell development.