Lineage choices in the developing thymus: choosing the T and NKT pathways

Thymic development proceeds through several defined stages that generate not only αβ and γδ T cells but can produce dendritic cells and B cells. The earliest thymocytes exist in the CD4−CD8− double negative compartment within a heterogeneous fraction termed DN1. Recent progress has identified several candidate populations that may be the bone fide T-cell progenitor population. The potential roles of these populations, which include hematopoietic stem cells, early lymphocyte precursors, common lymphoid progenitors, and early T lineage progenitors are being elucidated. The αβ T-cell lineage consists of distinct subsets, one of which is NKT cells. The developmental relationship of NKT cells to conventional T cells has been controversial. Recent work has shown that these cells are probably derived from CD4+CD8+ thymocytes. The discovery and application of CD1d tetramers has made it possible to more fully describe NKT-cell development.