Figure 1.

Schematic of T-cell development in the thymus. Major landmarks for T cell developmental stages are CD4 and CD8. CD4⁻ CD8⁻: “DN”; CD4⁺ CD8⁺: “DP,” CD4⁺ CD8⁻: “CD4SP”; CD4⁻ CD8⁺: “CD8SP.” All events described in this review occur within the DN stages, which are divided by other markers. ETP: Kit⁺⁺ CD44⁺ CD25⁻; DN2a: Kit⁺⁺ CD44⁺ CD25⁺; DN2b: Kit⁺ CD44⁺ CD25⁺; DN3a: Kit⁻ CD44⁻ CD25⁺ CD28⁻; DN3b: Kit⁻ CD44⁻ CD25⁺ CD28⁺; DN4: Kit⁻ CD44⁻ CD25⁻ CD28⁺. Stages up through DN3a do not depend on T-cell receptor gene rearrangement status and are called “Pro-T cells.” Many cell cycles occur between the ETP stage and commitment, more in post-natal T cell development and fewer in fetal T-cell development. The trends in PU.1 expression, the timing of intrinsic cell commitment to the T-cell lineage, and the stages that depend on Notch signaling from the thymic microenvironment are shown. Gray or blue regions depict thymic cortex. Lighter region depicts thymic medulla, where final maturation of developing T cells takes place. CD4SP: maturing T helper cells. CD8SP: maturing T cytotoxic cells. Treg: thymically derived regulatory T cells. iNKT: Natural Killer T cells with invariant T cell receptors [Schematic adapted from Rothenberg et al. (34)].