A guide to thymic selection of T cells

The thymus is an evolutionarily conserved organ that supports the development of T cells. Not only does the thymic environment support the rearrangement and expression of diverse T cell receptors but also provides a unique niche for the selection of appropriate T cell clones. Thymic selection ensures that the repertoire of available T cells is both useful (being MHC-restricted) and safe (being self-tolerant). The unique antigen-presentation features of the thymus ensure that the display of self-antigens is optimal to induce tolerance to all types of self-tissue. MHC class-specific functions of CD4+ T helper cells, CD8+ killer T cells and CD4+ regulatory T cells are also established in the thymus. Finally, the thymus provides signals for the development of several minor T cell subsets that promote immune and tissue homeostasis. This Review provides an introductory-level overview of our current understanding of the sophisticated thymic selection mechanisms that ensure T cells are useful and safe. This Review summarizes how the processes of thymic selection together ensure that the T cell repertoire is fully functional and safe. In the thymus, T cell receptor signal strength is integrated with distinct stromal cues to result in positive or negative selection of thymocytes or the generation of regulatory cells.