Isolation and Characterization of Murine Early Intrathymic Precursor Populations

The earliest steps along the pathway leading to mature T cells in mouse thymus have been defined ( 1 , 2 ). Within the thymus, several minute but discrete populations of T cell precursors develop in sequence, preceding the stage of CD4 + 8 + thymocytes (Fig. 1 ). The earliest identifiable intrathymic precursors in the adult mouse, termed “low CD4” precursors, express low levels of CD4 and Thy-1, and are positive for Sca-1, Sca-2, CD44 and c-kit but negative for CD25 ( 3 ). This precursor population represents only 0.03–0.05% of total thymocytes. It is not exclusively T-lineage committed and retains the potential to form NK cells, B cells and dendritic cells (DC) ( 4 – 6 ). The low CD4 precursor population then loses surface CD4 and develops into CD3 − 4 − 8 − triple negative (TN) precursors. Among the TN precursors, four subpopulations, representing 2–3% of total thymocytes, can be characterized by the early expression of CD44 and c-kit, and by transient expression of CD25. The developmental progression, deduced from precursor activities, is c-kit + CD44 + CD25 − −>c-kit + CD44 + CD25 + −>c-kit − CD44 − CD25 + −>c-kit − CD44 − CD25 − ( 7 – 10 ). The earliest c-kit + CD44 + CD25 − TN subpopulation, although believed to be more mature than the low CD4 precursors, has many features overlapping those of the low CD4 precursors. It also retains the potential to develop into NK cells, B cells and DC (L. Wu, unpublished observations).   Fig. 1.  A summary of the pathway of intrathymic T cell development. The precursor sequence was deduced based on the state of TCR gene rearrangement, the precursor activity and developmental kinetics of each precursor population ( 3 , 5 , 6 , 8 , 9 ). The proportion of each precursor population amongst all thymocytes is an average value for C57BL/6 mice.