Acute cell-mediated rejection in orthotopic pig-to-mouse corneal xenotransplantation

Abstract

Abstract: Background: To investigate the role of T cells and natural killer (NK) cells in mediating corneal xenograft rejection in a pig-tomouse model. Methods: Pig corneas were orthotopically transplanted into BALB/c, C57BL/6, nude, severe combined immunodeficiency (SCID), and NOD/ SCID/ccnull (NOG) mice. Graft survival was clinically assessed by slitlamp biomicroscopy and median survival times (MST) were calculated. The rejected grafts were histologically evaluated using antibodies against CD4, CD8, NK1.1, and F4/80. Results: The pig corneal xenografts were acutely rejected by BALB/c and C57BL/6 mice (MST 9.0 days), while nude, SCID and NOG mice rejected pig corneas in a more delayed fashion (MST 16.0, 16.4, and 16.9 days, respectively). The majority of infiltrating cells found in rejected grafts in C57BL/6 mice were macrophages and CD4+ T cells, while CD8+ T cells and NK cells were rarely found. The grafts in nude mice had markedly decreased inflammatory infiltration with small numbers of macrophages and CD4+ T cells. Infiltration was even more modest in grafts in SCID and NOG mice. Conclusions: T cells play an important role in acute rejection of pig corneal xenografts in mice, although acute rejection is not solely the result of T-cell-mediated immunity. NK cells are less likely to be involved in the rejection process.