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W. Wee, J. Oh, M. Kim, H. Lee, J. Ko, C.-S. Park, Y. Kim, J. Lee; The Role of T Cells, NK Cells, Antibodies, and Complements in Acute Rejection After Pig-to-Mouse Corneal Xenotransplantation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1971.
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To investigate the role of T cells, NK cells, Antibodies, and Complements in mediating corneal xenograft rejection in a pig-to-mouse model.
This study was approved by the Institutional Review Board and Institutional Animal Care and Use Committee of the Seoul National University Hospital, and also performed according to ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Porcine corneas from miniature pigs were transplanted to BALB/c, C57BL/6, SCID, NOG, and GTKO mice with or without complement depletion by cobra venom factor. Graft survival was clinically assessed by slit-lamp biomicroscopy, and median survival times (MST) were calculated. The peripheral blood and draining cervical lymph nodes were examined weekly for CD3, CD19, CD4, CD8, NK1.1, F4/80 by FACS. The rejected grafts were histologically evaluated using antibodies against CD4, CD8, NK1.1, C5b-9, and F4/80. The expression of various cytokines was also analyzed in the rejected grafts using ELISA.
The pig corneal xenografts were acutely rejected by BALB/c and C57BL/6, while SCID and NOG mice rejected pig corneas in a more delayed fashion. The graft survival was increased in WT mice with complement depletion. The majority of infiltrating cells in rejected grafts in C57BL/6 mice were innate cells including macrophages and neutrophils. Many CD4+ T cells were also infiltrated. Only small number of CD8+ T cells and NK cells were found. The grafts in SCID and NOG mice had markedly decreased inflammatory infiltration with macrophages. The WT mice depleted of complement had also significantly decreased infiltration of immune cells.
T cell and complement play a role in acute rejection of pig corneal xenografts in mice. However, suppression of innate cells such as macrophages and neutrophils is necessary to prolong the graft survival.
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