The role of natural killer cells in human solid organ and tissue transplantation

Abstract

During the last decade, considerable progress was made in the understanding of the natural killer (NK) cell mechanisms of action, especially in the processes of target cell recognition and lysis. These breakthroughs have aroused large interest in the role of NK cells in the pathogenesis of a variety of diseases. In hematopoietic stem cell transplantation, NK cells have been shown to play a significant role in the graft-versus-leukemic effect leading to protocols of cell therapy using amplified NK cells after transplantation. In human solid organ transplantation (SOT), the role of NK cells was controversial due to conflicting clinical and animal model data. NK cells have been shown to exacerbate T-cell responses during rejection, but also to promote tolerance induction under immunosuppression. The role of NK cells is of special interest in SOT because in contrast to T cells, the effect of immunosuppressive drugs on NK cells is modest, at least in vivo. Recent publications demonstrated the importance of killer cell immunoglobulin-like receptor/human leukocyte antigen genotypes to predict the risk of rejection and to prevent cytomegalovirus infection/reactivation. NK cell subpopulations could have different alloreactivity or immunomodulatory potentials. Finally, an understanding of the role of NK cells in the field of embryonic stem cells and their progenitor transplantation is developing. Currently, NK cells are considered a key player in the alloimmune and anti-infectious responses after SOT and transplanted tissues.