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.

Novel Combination of Surface Markers for the Reliable and Comprehensive Identification of Human Thymic Epithelial Cells by Flow Cytometry: Quantitation and Transcriptional Characterization of Thymic Stroma in a Pediatric Cohort

“…Recent analysis of cultured human TECs also indicated a partly shared gene expression signature between TECs and mesenchymal cells (70). The picture emerging from these studies (reviewed in (6) and our results demonstrate that non-hematopoietic stromal cells (TECs, FB and EC) participate in a complex division of labor with partly overlapping functions similar to what has been described for secondary lymphoid organs (44).…”

“…Throughout the thymus, a complex network of non-hematopoietic and hematopoietic accessory cells (including fibroblasts, endothelial cells, dendritic cells and macrophages) is organized within the two thymic compartments with dedicated functions ( 6 ). Those cells share tasks linked to the generation of T cells ( 7 , 8 ), but also support the differentiation and maintenance of TECs ( 9 , 10 ).…”

The thymic microenvironment gradually modulates the phenotype of thymus-homing peripheral conventional dendritic cells

“…43 For the intrathymic maturation and homeostasis of cDCs, mTECs were reported to play an only minor role. 44,45 Thus, although it is known that the heterogeneity of TECs is completed only in adulthood, 46,47 it is unlikely that the observed clear differences in the TEC compartment between embryonic thymi in RTOCs and ex vivo isolated adult thymi have a considerable effect on the modulation of sp-DCs. By contrast, different groups recently proposed that cognate interactions of antigen-specific CD4SP thymocytes with both resident and migratory t-DCs efficiently support the homeostatic maturation of t-DCs.…”

The fibroblast: An emerging key player in thymic T cell selection

“…The thymus is an organ in which T cells develop and their antigen recognition repertoire is established 1 . In the three‐dimensional microenvironment composed of thymic stromal cells, immature T cells (called thymocytes) undergo stepwise developmental processes, including differentiation, proliferation, and cell fate determination in order to give rise to mature T cells expressing a diverse T cell receptor (TCR) repertoire 2 …”

“…1 In the three-dimensional microenvironment composed of thymic stromal cells, immature T cells (called thymocytes) undergo stepwise developmental processes, including differentiation, proliferation, and cell fate determination in order to give rise to mature T cells expressing a diverse T cell receptor (TCR) repertoire. 2 The thymus parenchyma is subdivided into two regions, the cortex and medulla, wherein distinct subsets of thymic epithelial cells (TECs) form a reticular meshwork that houses developing thymocytes. 3,4 The cortex is the outer region with cortical TECs (cTECs) and thymocytes of immature stages, while the medulla is the inner region and is characterized by medullary TECs (mTECs) and mature thymocytes (Figure 1A).…”