Xenograft rejection and the innate immune system

Abstract

Purpose of review Major advances have been made in the understanding of the immune mechanisms underlying hyperacute and acute vascular xenograft rejection. Key roles of T and B lymphocytes have been revealed and significant progress has been made in understanding how they contribute to xenograft rejection and how they can be tolerized. In addition to the well established contribution of naturally occurring anti-Galα1,3Galβ1,4GlcNAc antibodies, the importance of active participation in xenograft rejection by other components of the innate immune system is increasingly being acknowledged. Recent findings Naturally occurring anti-Galα1,3Galβ1,4GlcNAc antibodies and complement play a central role in hyperacute xenograft rejection and are also involved in acute vascular xenograft rejection. Reports indicate that natural killer cells can contribute to xenograft rejection, and several mechanisms of action have been proposed. Furthermore, evidence indicates that macrophages and neutrophils are able to directly recognize xenogeneic target cells and to directly mediate xenograft damage. Although a role of Toll-like receptor signalling in allograft rejection is emerging, data on its role in xenograft rejection are limited. Summary Several components of the innate immune system can actively participate in xenograft rejection and thus represent a barrier to xenograft acceptance that may be particularly difficult to overcome.