Thymic Crosstalk: An Overview of the Complex Cellular Interactions that Control the Establishment of T-Cell Tolerance

The thymus ensures the generation of a self-tolerant T-cell repertoire capable of recognizing foreign antigens. The selection of the T-cell repertoire is dictated by the thymic microenvironment. Among stromal cells, medullary thymic epithelial cells (mTECs) play a pivotal role in this process through their unique ability to express thousands of tissue-restricted self-antigens. In turn, developing T cells control the pool and maturation of mTECs. This phenomenon of bidirectional interactions between TECs and thymocytes is referred to as thymic crosstalk. In this chapter, I discuss the discovery of thymic crosstalk and our current understanding of bidirectional interactions between mTECs and thymocytes. Finally, I summarize recent advances indicating that thymic crosstalk is not restricted to TECs and thymocytes but also occurs between TECs and dendritic cells, as well as B cells and thymocytes. This complex cellular interplay is essential for efficient T-cell selection.