Cutting edge: NKT cell development is selectively impaired in Fyn-deficient mice

Most NK1.1(+) T (NKT) cells express a biased TCR alpha beta 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 con trast to conventional T cells, requires positive selection by cells of hemo poietic origin. Here, we show that the Src protein tyrosine kinase Fyn is r equired for development of CD1d-dependent NKT cells but not for the develop ment of conventional T cells. In contrast, another Src kinase, Lck, is requ ired for the development of both NKT and T cells. Impaired NKT cell develop ment in Fyn-deficient mice cannot be rescued by transgenic expression of CD 8, which is believed to increase the avidity of CD1d recognition by NKT cel ls. Taken together, our data reveal a selective and nonredundant role for F yn in NKT cell development.