The contributions of T-cell anergy to peripheral T-cell tolerance.

Intrathymic deletion of thymocytes with high af®nity for self antigen cells plays a crucial role in contracting the autoreactive T-cell repertoire. However, this is manifestly an incomplete process. Not all self proteins are effectively presented in the thymus, including those that are expressed well after the bulk of the T-cell repertoire has been formed, and it is relatively easy to detect autoreactive T cells following immunization with self antigens. For this reason mechanisms of regulating peripheral T cells with unwanted speci®city are crucial to survival. There are several mechanisms of peripheral T-cell unresponsiveness including ignorance, deletion by apoptosis, and cytokinemediated regulation. The topic of this review is a further mechanism, T-cell anergy. Data will be highlighted, which suggests that the induction of T-cell anergy is an important contributor to peripheral T-cell tolerance, and that anergic T-cells are not passive, but may play an important role as regulatory cells.