TRIGGERING OF NATURAL-KILLER-CELLS BY THE COSTIMULATORY MOLECULE CD80(B7-1)

NK cell-mediated cytotoxicity is influenced by triggering as well as i nhibitory signals. The identification of inhibitory signals provided b y MHC class I molecules has recently attracted significant attention. Much less is known about putative triggering signals. Using purified p opulations of mouse NK cells, we demonstrate that the CD80 (B7-1) gene product functions as a triggering signal for NK cell-mediated cytotox icity. The strength of this response is such that it overrides the pro tection mediated by MHC class I molecules. Triggering of mouse NK cell s by B7-1 occurred even in the absence of CD28 and could not be blocke d by either anti-CD28 or anti-CTLA-4 antibodies. NK cells may thus, at least in part, use receptors other than CD28 and CTLA-4 in their inte raction with B7-1. Furthermore, we demonstrate that bone marrow-derive d macrophages and dendritic cells are highly susceptible to lysis by a utologous NK cells.