Natural killer cells in rejection and tolerance of solid organ allografts

A series of recent studies defy conventional wisdom by showing that natural killer (NK) cells exert a powerful and long-lasting influence on the immune response to whole organ allografts. The early activation of NK cells following transplantation is associated with killing of allogeneic target cells and release of immunomodulatory chemokines and cytokines, which can contribute to either rejection or tolerance. Here, we review findings describing NK cell receptors, potential mediators and mechanisms underlying the dual influence of NK cells in solid organ transplantation.

New studies show that NK cells can discriminate between self and foreign tissues and play a key role in the initiation and regulation of adaptive immune responses after solid organ transplantation. Depending upon the types of NK cell receptors engaged and the nature of cytokines released, early NK cell activation can promote either rejection or tolerance.

Solid organ transplantation is associated with the early activation of NK cells, which are then licensed to kill allogeneic target cells directly or via antibody-dependent cellular cytotoxicity and release various chemokines and immunomodulatory cytokines. Depending upon the nature of NK cell subsets activated and their ability to kill allogeneic target cells and release certain types of cytokines, NK cells can promote the activation/expansion of pro-inflammatory Th1 cells or regulatory Th2/Treg cells thus tilting the balance of alloimmunity towards rejection or tolerance. An in-depth understanding of these mechanisms will be necessary in order to design therapies targeting NK cells in human transplantation.