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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. |
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