Triggering of natural killer cells by the costimulatory molecule CD80 (B7-1)

NK cell-mediated cytotoxicity is influenced by triggering as well as inhibitory signals. The identification of inhibitory signals provided by MHC class I molecules has recently attracted significant attention. Much less is known about putative triggering signals. Using purified populations of mouse NK cells, we demonstrate that the CD80 (B7-1) gene product functions as a triggering signal for NK cell-mediated cytotoxicity. The strength of this response is such that it overrides the protection mediated by MHC class I molecules. Triggering of mouse NK cells by B7-1 occurred even in the absence of CD28 and could not be blocked 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 interaction with B7-1. Furthermore, we demonstrate that bone marrow-derived macrophages and dendritic cells are highly susceptible to lysis by autologous NK cells.