**4.7 Role of natural killer cells**

Natural killer (NK) cells are important in transplantation because of their ability to distinguish allogenic cells from self and their potent cytolytic effector mechanisms. These cells can mount maximal effector responses without any prior immune sensitization. Unlike T and B cells, NK cells are activated by the absence of MHC molecules on the surface of target cells, which is commonly referred to as the "missing self" hypothesis. Recognition is mediated by various NK inhibitory receptors triggered by specific alleles of MHC class I antigens on cell surfaces.

In addition, NK cells also possess stimulatory receptors, which are triggered by antigens on nonself cells. NK cell effector responses include both cytokine release and direct toxicity mediated through perforin, granzymes, Fas ligand (FasL), and TNF-related apoptosisinducing ligand (TRAIL). Through this "double negative" mode of activation, they are thought to play a role in the rejection of both bone marrow transplants and transplanted lymphomas in animal models.

NK cells also provide help to CD28-positive host T cells, thereby promoting allograft rejection. Their importance in bone marrow transplants has been recognized for years. In humans, the NK cell-mediated graft-versus-host alloresponse has been used for its potent graft-versus-leukemia effect, contributing to an increase in the rate of sustained remission in patients with acute myelogenous leukemia[11].

NK cells are now being recognized as active participants in acute and chronic rejection of solid tissue grafts. Recent studies have indicated that NK cells are present and activated following infiltration into solid organ allografts. They may regulate cardiac allograft outcomes. Studies have also shown that humans with killer cell immunoglobulin-like receptors that are inhibited by donor MHC have a decreased risk of liver transplant rejection. In cases of renal transplantation, NK cells are not suppressed by the current immunosuppressive regimens[13].
