Acute cell-mediated rejection in orthotopic pig-to-mouse corneal xenotransplantation |
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Authors: | Joo Youn Oh Mee Kum Kim Jung Hwa Ko Hyun Ju Lee Youngji Kim Chan-Sik Park Chung-Gyu Park Sang Joon Kim Won Ryang Wee Jin Hak Lee |
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Institution: | Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute;, Department of Ophthalmology, Seoul National University College of Medicine;, Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital;, Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine;, Department of Microbiology and Immunology, Seoul National University College of Medicine;, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea |
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Abstract: | Abstract: Background: To investigate the role of T cells and natural killer (NK) cells in mediating corneal xenograft rejection in a pig-to-mouse model. Methods: Pig corneas were orthotopically transplanted into BALB/c, C57BL/6, nude, severe combined immunodeficiency (SCID), and NOD/SCID/γcnull (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. 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. |
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Keywords: | cornea mouse pig rejection xenotransplantation |
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