A natural killer T (NKT) cell developmental pathway involving a thymus dependent, NK1.1-CD4+ CD1d-dependent precursor stage

Abstract

The development of CD1d-dependent natural killer T (NKT) cells is poorly understood. We have used both CD1d/-galactosylceramide (CD1d/GC) tetramers and anti-NK1.1 to investigate NKT cell development in vitro and in vivo. Confirming the thymus-dependence of these cells, we show that CD1d/GC tetramer-binding NKT cells, including NK1.1 and NK1.1 subsets, develop in fetal thymus organ culture (FTOC) and are completely absent in nude mice. Ontogenically, CD1d/GC tetramer-binding NKT cells first appear in the thymus, at day 5 after birth, as CD4 CD8 NK1.1 cells. NK1.1 NKT cells, including CD4 and CD4 CD8 subsets, appeared at days 7–8 but remained a minor subset until at least 3 wk of age. Using intrathymic transfer experiments, CD4 NK1.1 NKT cells gave rise to NK1.1 NKT cells (including CD4 and CD4 subsets), but not vice-versa. This maturation step was not required for NKT cells to migrate to other tissues, as NK1.1 NKT cells were detected in liver and spleen as early as day 8 after birth, and the majority of NKT cells among recent thymic emigrants (RTE) were NK1.1

Further elucidation of this NKT cell developmental pathway should prove to be invaluable for studying the mechanisms that regulate the development of these cells.