Figure 6. Differentiation and Maturation of T Cells in the Thymus.

Hematopoietic stem cells which do not express CD3, CD4 or CD8 but which are committed to T cell differentiation move from the bone marrow to the thymic subcapsular zone. There they begin rearrangement of the TCR genes. Once a productive TCR β chain has been produced, they move the thymic cortex where TCR α chain rearrangement occurs and surface expression of the CD3, CD4 and CD8 proteins is induced. These CD4⁺CD8⁺ (‘double positive’) cells are positively selected on cortical epithelial cells for their ability to recognize self Class I or Class II HLA proteins. If the developing T cell has adequate affinity to recognize a self Class I protein, then it retains expression of CD8 and extinguishes expression of CD4. If the cell recognizes a self Class II protein, then it retains expression of CD4 and extinguishes expression of CD8. Selected CD4/CD8 single positive (SP) cells then move to the thymic medulla where they are negatively selected on medullary epithelial cells to remove cells with excessive affinity for self-antigens presented in HLA molecules. Cells emerge from positive selection SP for CD4 or CD8 expression and then are exported to the periphery. Cells that fail positive or negative selection are removed by apoptosis. A small fraction of cells differentiate from to rearrange their TCR γ and δ chains, rather than their TCR α and β chains. Modified with permission from Huston.¹¹⁴