Possible mechanisms of NK cell–mediated acute GVHD. Subclinical GVHD triggers NK cell activation through unknown mechanisms (denoted by “?”), perhaps involving antiepithelial antibodies or expression of stress ligands induced by local inflammation. The resulting NK-cell responses may be targeted directly at epithelial cells (1), or may indirectly activate adaptive immune mechanisms that exacerbate T-cell–mediated GVHD (2-5). Professional illustration by Luk Cox.