Natural killer cell subsets in allograft rejection and toleranceAlegre, Maria-Luisa; McNerney, Megan ECurrent Opinion in Organ Transplantation: February 2007 - Volume 12 - Issue 1 - p 10–16 doi: 10.1097/MOT.0b013e3280129f2a Mechanisms of rejection Abstract Author Information Purpose of review To discuss the role of natural killer cells in regulating the survival of transplanted organs. Recent findings Natural killer cells have been found to have the dual capacity to promote rejection of transplanted organs and be required for the induction of transplantation tolerance. In murine recipients of bone marrow transplants, or in CD28−/− recipients of cardiac allografts, different natural killer cell subsets have been shown to promote or delay rejection, depending on their major histocompatibility complex class I specificity. In mouse models of skin and islet allograft acceptance mediated by costimulation-targeting therapies, the presence of natural killer cells was found to be essential for long-term graft acceptance, perhaps due to their ability to eliminate donor or recipient immune cells. Summary Natural killer cells can either accelerate or avert rejection in a manner that is influenced by both donor–recipient major histocompatibility complex disparity as well as the milieu created by costimulation-targeting therapies. In clinical settings, alloreactivity by defined natural killer cell subsets may be important in achieving tolerance, and the outcome of natural killer cell activity may be influenced by specific immunosuppressive regimens. The University of Chicago, Department of Medicine, Chicago, Illinois, USA Correspondence to Maria-Luisa Alegre, MD, PhD, University of Chicago, 5841 S Maryland Avenue, MC0930, Chicago, IL 60637, USA Tel: +1 773 834 4317; fax: +1 773 702 8702; e-mail: firstname.lastname@example.org © 2007 Lippincott Williams & Wilkins, Inc.