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A Natural Killer T (NKT) Cell Developmental Pathway Involving a Thymus-dependent NK1.1 CD4 CD1d-dependent Precursor Stage

Daniel G. Pellicci, et al.

J. Exp. Med. The Rockefeller University Press • 0022-1007/2002/04/835/10 $5.00

Volume 195, Number 7, April 1, 2002 835–844

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 CD4CD8NK1.1cells. 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 NK1.1NKT 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.

Cutting Edge: NKT Cell Development IsSelectively Impaired in Fyn- Deficient Mice. J Immunol 1999; 163:4091-4094.

Gérard Eberl, et al.

Most NK1.11 T (NKT) cells express a biased TCRab repertoire that is positively selected by the monomorphic MHC class I-like molecule CD1d. The development of CD1d-dependent NKT cells is thymus dependent but, in contrast to conventional T cells, requires positive selection by cells of hemopoietic origin. Here, we show that the Src protein tyrosine kinase Fyn is required for development of CD1d-dependent NKT cells but not for the development of conventional T cells. In contrast, another Src kinase, Lck, is required for the development of both NKT and T cells. Impaired NKT cell development in Fyndeficient mice cannot be rescued by transgenic expression of CD8, which is believed to increase the avidity of CD1d recognition by NKT cells. Taken together, our data reveal a selective and nonredundant role for Fyn in NKT cell development.