The roles of T and natural killer cells in a pig‐to‐mouse corneal xenotransplantation

Abstract

Purpose To determine the role of T cells and natural killer (NK) cells in mediating corneal xenograft rejection of a pig‐to‐mouse model. Methods Pig corneas were orthotopically transplanted to C57BL/6, Balb/c‐nu and CB.17 SCID mice with or without NK depletion. NK cells were depleted by an intraperitoneal injection of anti‐NK1.1 mAb three days before and one day after transplantation. Graft survival was clinically assessed by slit‐lamp microscopy, and median survival times (MST) were calculated. The rejected grafts were histologically evaluated. Results The pig corneal xenografts were acutely rejected by C57BL/6 mice (MST 7.00±0.61 days), while Balb/c‐nu and CB.17 SCID mice rejected pig corneas in more delayed fashion (MST 14.00±0.77 and 15.00±0.58 days, respectively). NK depletion failed to a further prolongation of the pig corneal xenograft survival in Balb/c‐nu mice. The rejected grafts in C57BL/6 mice were heavily infiltrated with inflammatory cells, the majority of which were macrophages. Many CD4+ T cells were observed, but either CD8+ T cells or NK cells were rarely found. In contrast, the grafts in Balb/c‐nu mice had markedly decreased inflammatory infiltration with small amounts of macrophages and CD4+ T cells, and the infiltration was further reduced in CB.17 SCID mice. Conclusion Acute rejection of the pig corneal xenografts in mice is not solely a consequence of an adaptive immunity although CD4+ T cells play an important role in the graft rejection. Other innate immune effectors than NK cells seem to be involved in the rejection of a pig‐to‐mouse corneal xenotransplantation.