A 2020 View of Thymus Stromal Cells in T Cell Development

Abstract

The thymus is an intricate primary lymphoid organ, wherein bone marrow-derived lymphoid progenitor cells are induced to develop into functionally competent T cells that express a diverse TCR repertoire, which is selected to allow for the recognition of foreign Ags while avoiding self-reactivity or autoimmunity. Thymus stromal cells, which can include all non-T lineage cells, such as thymic epithelial cells, endothelial cells, mesenchymal/fibroblast cells, dendritic cells, and B cells, provide signals that are essential for thymocyte development as well as for the homeostasis of the thymic stroma itself. In this brief review, we focus on the key roles played by thymic stromal cells during early stages of T cell development, such as promoting the homing of thymic-seeding progenitors, inducing T lineage differentiation, and supporting thymocyte survival and proliferation. We also discuss recent advances on the transcriptional regulation that govern thymic epithelial cell function as well as the cellular and molecular changes that are associated with thymic involution and regeneration.

Figure 1.

Intrathymic interplay between stromal cells and developing thymocytes. A schematic overview of T cell development is shown, with incoming thymic seeding progenitors (TSPs) extravasating into the thymus at the cortico-medullary junction, wherein they migrate through the cortex and differentiate into distinct CD4⁻CD8⁻ double negative (DN) subsets, as indicated. Later stages, immature single positive (ISP) and CD4⁺CD8⁺ double positive (DP) stages continue to differentiate, undergoing positive selection, and give rise to CD4 and CD8 single positive (SP) cells that enter the medulla to under negative selection and final maturation before exiting the thymus, as indicated. Key interacting stromal cells and molecules are shown and indicated.