Innate cellular immunity and xenotransplantation

Abstract

Purpose of review: This review assesses the recent progress in xenograft rejection by innate immune responses, with a focus on innate cellular xenoreactivity.

Recent findings: Current literature was reviewed for new insights into the role of innate cellular immunity in xenograft rejection. Increasing evidence confirms that vigorous innate immune cell activation is accounted for by a combination of xenoantigen recognition by activating receptors, and incompatibility in inhibitory receptor-ligand interactions. Although both innate humoral and cellular xenoimmune responses are predominantly elicited by preformed and induced xenoreactive antibodies in nonhuman primates following porcine xenotransplantation, innate immune cells can also be activated by xenografts in the absence of antibodies. The latter antibody-independent response will likely persist in recipients even when adaptive xenoimmune responses are suppressed. In addition to xenograft rejection by recipient innate immune cells, phagocytic cells within liver xenografts are also deleterious to recipients by causing thrombocytopenia.

Summary: Strategies of overcoming innate immune responses are required for successful clinical xenotransplantation. In addition to developing better immunosuppressive and tolerance induction protocols, endeavors towards further genetic modifications of porcine source animals are ultimately important for successful clinical xenotransplantation.

Figure 1. CD47-deficient skin grafts survived long-term with no sign of rejection at histology in syngeneic CD47-competent mice

Wild-type (WT) B6 mice were grafted with CD47 KO and WT (control) B6 skin. Shown are representative histological sections (H&E) of skin grafts at weeks 2 and 10 post-transplantation.