Antigenicity of porcine cornea in xenocorneal transplantation

초록

Purpose: To investigate antigenicity and immuno logical rejection in porcine-to-murine xenotransplantation as indicator of biofeasibility of the porcine xenograft for human substitute. Materials and Methods: The alpha-Gal epitope in corneal tissue and cultured porcine cells was stained with Griffonia simplicifolia 1 isolectin B4. Porcine corneas was orthotopically transplanted to rats. Graft survival, hematoxylin and eosin, CD4 or CD8 staining, and enzyme-linked immunosorbent assays for interleukins and interferon-gamma were evaluated. Cultured porcine keratocytes and endothelial cells were mixed with human sera or peripheral blood mononuclear cells for 72 hours. The amount of complement deposited in cells and the number of 51-chromium-releasing cells were assessed. Gene expression was comparatively analyzed using Platinum pig 13K oligo chip in cultured porcine keratocytes and porcine endothelial cells. Results: The distribution of alpha-Gal epitope was localized to the anterior stromal keratocytes. However, alpha-Gal was highly expressed in keratocytes and endothelial cells after cultivation. Median survival of porcine grafts was 8 days. Neutrophils and monocytes were prominent in stroma. The number of CD8(+) cells was higher than that of CD4(+) cells. Interleukin-2 and interferon-gamma markedly increased in cornea, lacrimal glands, and cervical lymph nodes after 10 days. Complement deposition and the number of 51-chromium-releasing cells were significantly higher in keratocytes than in endothelial cells. TNFAIP6. CXCL14, and CXCL6 genes were highly expressed in keratocytes compared with in endothelial cells. Conclusion: Porcine-to-rat orthotopic corneal xenograft showed CD8(+) cell- and innate immune cell-related stromal rejection, suggesting, high cytotoxicity of porcine keratocytes.

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