Natural killer cell subsets in allograft rejection and tolerance

Curr Opin Organ Transplant. 2007 Feb;12(1):10-16. doi: 10.1097/MOT.0b013e3280129f2a.


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.