The innate natural killer cells in transplant rejection and tolerance induction

Abstract

The roles of adaptive immune cells in transplant models have been extensively studied, but very little is known about the role of innate immune cells in the allograft response, especially in tolerance induction. In this review, we summarized the latest developments in the study of the role of natural killer cells in mediating graft rejection and tolerance induction. Natural killer cells are potent cytolytic cells; they also induce tissue inflammation by producing powerful proinflammatory cytokines. Thus, natural killer cells can act as effector cells in transplant rejection. Recent studies, however, have demonstrated additional roles for natural killer cells in the induction of transplant tolerance. We found that natural killer cells control survival of graft-derived donor cells and killing of donor dendritic cells by host natural killer cells inhibits direct priming of alloreactive T cells. Natural killer cells are also shown directly to suppress the activation of T cells. In other models, natural killer cells are found to regulate the induction of regulatory T cells. These new findings may have important clinical implications in tolerance induction. Natural killer cells are involved in both graft rejection and tolerance induction; such opposing effects may be mediated by differences in the activation status of natural killer cells. We believe that natural killer cells can be therapeutically modified for the induction of transplant tolerance.