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The effects of passive transfer of antisera containing cytotoxic antibodies to allo- and xenoantigens on survival of corneal allografts and xenografts were evaluated in experimental models. Corneas from allogeneic B10 or xenogeneic rat Lewis donors were grafted orthotopically into BALB/c mice. Recipient mice were treated with donor-specific antisera administered at the period of grafting or at 2 weeks after transplantation. Rejection was determined by the severity of corneal opacity using a standard scoring system. Treatment of graft recipients with donor-specific antisera accelerated the onset of graft rejection and significantly shortened survival times of both corneal allografts and xenografts. Corneal xenografts, which had been accepted after treatment with anti-CD4 monoclonal antibody, were acutely rejected by the passive transfer of antiserum against xenoantigens. The results suggest that corneal grafts are vulnerable to antibody-dependent immunity and that cytotoxic antibodies against graft donor antigens can mediate rejection of both corneal allografts and xenografts.

Corneal xenotransplantation may be an alternative approach to overcome shortage of allografts for clinical transplantation. Orthotopic corneal rat-to-mouse xenotransplantation and syngeneic transplantation was performed and the effects of anti-CD4 and anti-CD8 treatments on corneal xenograft survival and production of cytokines, interleukin (IL)-2, IL-4, IL-10, gamma-interferon (IFN-gamma) and nitric oxide (NO) were evaluated. RT-PCR was used to determine the expression of genes for cytokines and inducible nitric oxide synthase (iNOS) in the grafts. The presence of iNOS protein in grafts was detected by immunofluorescent staining. We found that corneal xenotransplantation was associated with a strong upregulation of genes for both Th1 and Th2 cytokines and with NO production in the graft. Treatment of xenograft recipients with mAb anti-CD4, but not anti-CD8, resulted in a profound inhibition of IL-2, IL-4 and IL-10 production, and in a significant prolongation of corneal xenograft survival. The results show that upregulation of Th2 cytokines after corneal xenotransplantation does not correlate with xenograft rejection. Rather, corneal graft rejection is associated with the expression of genes for IFN-gamma and iNOS and with NO production.