In the mouse allogeneic transplant setting, inflammatory cytokines prime NK cells to enhance their function so that U-NK cells containing inhibitory receptors matching cognate MHCI ligand in the graft secrete GM-CSF, which facilitates donor cell engraftment (A). U-NK cells whose inhibitory receptors do not recognize MHCI ligands on the graft (thus mismatched) drive graft rejection when previously primed (B). L-NK cells not encountering cognate MHCI ligands (missing self) mediate graft rejection (+), whereas tolerance (−) results if L-NK cells encounter cognate MHCI ligands (C). BMC, bone marrow cell; IFNγ, interferon-γ; IL-2, interleukin-2; iNKR, inhibitory NK cell receptor.