Thymic and Postthymic Regulation of Naïve CD4⁺ T-Cell Lineage Fates in Humans and Mice Models

Figure 1

Schematic representation of T-cell positive and negative selection along the differentiation and maturation of T-cell progenitors in the thymus. Expression and rearrangement of the T-cell receptor (TCR) genes and upregulation of CD4 and CD8 give rise to CD4⁺CD8⁺ double-positive (DP) thymocytes whose T-cell receptor binds to self-antigens presented by cortical thymic epithelial cells (cTECs). Insufficient affinity for self-MHC blocks intracellular signals for cell survival and leads to cell death and positive selection at the cortex. These cells migrate to the medulla, where they bind to tissue-restricted antigens (TRA) presented by medullary TECs (mTECs). Excessive affinity for self-peptides in the context of MHC will determine cell death of autoreactive T-cells and negative selection. Only a small fraction of T-cells survive and are exported to the periphery.