T-Cell Development

Progenitor T cells migrate from the fetal liver and later in the bone marrow into the thymus where they undergo a complex series of V(D)J rearrangement events, which enable them to create a highly diverse set of T cell receptors. After V(D)J rearrangement is complete, T cells are subjected to a series of selection events designed to promote the survival of TCR that can bind to MHC class I or class II molecules bearing self-peptides, but not too well. T cells bearing TCR that fail to bind (positive selection) or bind too well (negative selection) undergo apoptosis. Thymocytes that achieve expression of a functional TCR express both CD4 and CD8 (double positive, or DP). T cells that can use CD4 co-receptors to stabilize binding to self peptide-MHC class II molecules expressed by thymic cortical epithelial cells downregulate expression of CD8 and become single positive (SP) CD4 T helper cells; whereas T cells that can use CD8 to bind to self peptide-MHC class I molecules expressed on thymic cortical epithelial cells become CD8 T cytotoxic cells and down regulate CD4. Single positive mature thymocytes then emigrate to the periphery where they play a key role in adaptive immunity as mature T cells.