Selective induction of NK cell proliferation and cytotoxicity by activatedNKT cells

NK T cells produce cytokines when their semi-invariant TCR engages glycolip ids associated with CD1d. The physiological consequences of NKT cell activa tion remain controversial, although they have been implicated in control of autoimmunity, parasites and tumors. We show here that specific activation of NKT cells in liver and spleen leads to a rapid induction of extensive NK cell proliferation and cytotoxicity. This NK cell activation is dependent, at least in part, on IFN-gamma production by NKT cells and IL-12 productio n by antigen-presenting cells. Remarkably, activation of NK cells by NKT ce lls is highly selective, since bystander T and B lymphocytes show transient expression of activation markers but almost no proliferation. Collectively our data suggest that CD1d-dependent NKT cells regulate innate immunity by sampling blood-borne glycolipid antigens and rapidly activating NK cells.