English: A figure depicting the process of T cell / thymocyte positive and negative selection in the thymus

Figure legend

Lymphoid progenitors migrate from the bone marrow to the thymic cortex. Here they develop through a number of intermediate stages termed double-negative (DN) 1 to 4 where the cells remain negative for both the CD4 and CD8 co-receptors. During this process, the cells lose expression of CD44 and transiently express the IL2 receptor. There is rearrangement of the T cell receptor beta chain, and then if the beta chain successfully pairs with the pre-alpha chain, the alpha chain is rearranged, the cells proliferate and then enter a double-positive (DP) stage expressing the TCR, CD4 and CD8. Here, if the cells receive adequate signals through their TCR in response to antigenic sequences expressed by cortical thymic epithelial cells, they survive and are polarised towards persistent expression of either CD4 or CD8 depending on their specificity. If cells do not receive sufficient stimulation, they enter apoptosis: so-called death by neglect. Next, single-positive (SP) cells enter the thymic medulla and interact with self-antigens expressed on medullary thymic epithelial cells. The expression of otherwise tissue-restricted self antigens is mediated by AIRE and Fezf2. Cells that receive weaker signals adopt an effector phenotype, cells that receive intermediate signals adopt a regulatory phenotype whilst cells that receive strong signals from self antigen enter apoptosis