Acute cell-mediated rejection in orthotopic pig-to-mouse corneal xenotransplantation
Joo Youn Oh
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
Search for more papers by this authorMee Kum Kim
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
Search for more papers by this authorJung Hwa Ko
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
Search for more papers by this authorHyun Ju Lee
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
Search for more papers by this authorYoungji Kim
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine
Search for more papers by this authorChan-Sik Park
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine
Search for more papers by this authorChung-Gyu Park
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Microbiology and Immunology, Seoul National University College of Medicine
Search for more papers by this authorSang Joon Kim
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorWon Ryang Wee
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
Search for more papers by this authorJin Hak Lee
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
Search for more papers by this authorJoo Youn Oh
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
Search for more papers by this authorMee Kum Kim
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
Search for more papers by this authorJung Hwa Ko
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
Search for more papers by this authorHyun Ju Lee
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
Search for more papers by this authorYoungji Kim
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine
Search for more papers by this authorChan-Sik Park
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine
Search for more papers by this authorChung-Gyu Park
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Microbiology and Immunology, Seoul National University College of Medicine
Search for more papers by this authorSang Joon Kim
Xenotransplantation Research Center and Clinical Research Institute, Seoul National University Hospital
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorWon Ryang Wee
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
Search for more papers by this authorJin Hak Lee
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
Search for more papers by this authorAbstract
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.
Supporting Information
Figure S1. Immunofluorescence co-staining for CD3+CD4+ (C) and CD3+CD8+ cells (D) in rejected pig corneas grafted in B6 mice.
Figure S2. Immunofluorescence co-staining of CD4+ and CD8+ T cells in pig corneas grafted in B6 mice 1 week, 2 and 3 weeks after transplantation.
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