Frontiers in nephrology: the varied faces of natural killer cells in transplantation--contributions to both allograft immunity and tolerance.

Natural killer (NK) cells are recognized for providing an important early innate immune response to viral and bacterial pathogens and for the surveillance of stressed and transformed autologous cells. However, with the exception of a pronounced role in allogeneic hematopoietic stem cell rejection, it has been challenging to ascribe the precise roles for NK cells in reactivity to tissue and solid-organ transplants. In general, NK cells initiate a rapid, proinflammatory environment that is conducive to many forms of effective immune host defense. This reactivity is often considered deleterious to allograft survival because NK cells are implicated in promoting both acute and chronic graft injury. However, more recent findings indicate that NK cells can also play a surprisingly profound role in allograft tolerance induction. This duality of function requires a reconsideration of the nature and consequence of NK cell reactivity during the allograft response. This review focuses on the differing "faces" of NK cells, especially the unexpected role of NK cells in allograft tolerance induction.