Role of complement and NK cells in antibody mediated rejection

Abstract

Despite extensive research on T cells and potent immunosuppressive regimens that target cellular mediated rejection, few regimens have been proved to be effective on antibody-mediated rejection (AMR), particularly in the chronic setting. C4d deposition in the graft has been proved to be a useful marker for AMR; however, there is an imperfect association between C4d and AMR. While complement has been considered as the main player in acute AMR, the effector mechanisms in chronic AMR are still debated. Recent studies support the role of NK cells and direct effects of antibody on endothelium cells in a mechanism suggesting the presence of a complement-independent pathway. Here, we review the history, currently available systems and progress in experimental animal research. Although there are consistent findings from human and animal research, transposing the experimental results from rodent to human has been hampered by the differences in endothelial functions between species. We briefly describe the findings from patients and compare them with results from animals, to propose a combined perspective.

Fig. 1

Activation of NK cells through the CD16/FcγRIII (CD16) triggers increased maturation of NK cells, loss of CD56, expression of the transcription factor T-bet and production of cytokine mediators. One or more of these mechanisms is hypothesized to be involved in the induction of CAV by NK cells and antibody.