THYMUS-INDEPENDENT GENERATION OF NK1(-CELLS IN-VITRO FROM FETAL LIVERPRECURSORS() T)

NK1.1(+)TCR alpha beta(+) (NK1(+)) T cells are an unusual subset of mo use TCR alpha beta(+) cells found primarily in adult thymus and liver. In contrast to conventional TCR alpha beta(+) cells, NK1(+) T cells h ave a TCR repertoire that is highly skewed to V alpha 14 and to V beta 8, -7, and -2. The developmental origin and ligand specificity of NK1 (+) T cells are controversial. We show here that NK1(+) T cells with a typically biased V alpha and V beta repertoire develop in cytokine-su pplemented suspension cultures of fetal liver established from either normal or athymic mice. Furthermore, NK1(+)T cell development in fetal liver cultures is abrogated in beta(2)m-deficient mice (which lack MH C class I and other related molecules) and can be partially inhibited by the presence of anti-CD1 mAbs. Moreover, mixing experiments indicat e that recombination-deficient SCID fetal liver cells can reconstitute NK1(+) T cell development in beta(2)m-deficient fetal liver cultures. Collectively, our data demonstrate that NK1(+) T cells can develop ex trathymically from fetal liver precursors and that a beta(2)m-associat ed ligand (putatively CD1) present on nonlymphoid cells is essential f or their positive selection and/or expansion.