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

Abstract

Oh JY, Kim MK, Ko JH, Lee HJ, Kim Y, Park C-S, Park C-G, Kim SJ, Wee WR, Lee JH. Acute cell-mediated rejection in orthotopic pig-to-mouse corneal xenotransplantation. Xenotransplantation 2009; 16: 74-82. (C) 2009 John Wiley & Sons A/S. To investigate the role of T cells and natural killer (NK) cells in mediating corneal xenograft rejection in a pig-to-mouse model. Pig corneas were orthotopically transplanted into BALB/c, C57BL/6, nude, severe combined immunodeficiency (SCID), and NOD/SCID/gamma c(null) (NOG) mice. Graft survival was clinically assessed by slit-lamp biomicroscopy and median survival times (MST) were calculated. The rejected grafts were histologically evaluated using antibodies against CD4, CD8, NK1.1, and F4/80. 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. 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.