THE PRESENCE OF ACTIVATED DONOR HLA CLASS I-REACTIVE T-LYMPHOCYTES ISASSOCIATED WITH REJECTION OF CORNEAL GRAFTS

Although the cornea is considered to be an immunological privileged si te, corneal transplantation can result in immunological rejection foll owed by graft failure, especially in patients with vascularized cornea s. Several studies suggest a beneficial effect of matching for the HLA class I antigens on corneal graft survival, although a large study (t he Collaborative Corneal Transplantation Study) failed to confirm this . To circumvent an endless discussion on studies either confirming or denying the relevance of HLA matching, we decided to approach this pro blem in another way. A more direct way to assess the importance of HLA class I antigens in corneal transplantation is to measure whether rej ection of an allograft is associated with priming of cytotoxic T lymph ocytes recognizing the mismatched HLA antigens of the donor. In the pr esent study, 13 patients with good graft function and 10 with ongoing rejection of their corneal allografts were analyzed for the presence o f CTL directed against mismatched donor HLA class I antigens, by limit ing dilution assays. CTLs were divided into naive and primed CTLs base d on the measurement of their in vitro sensitivity or resistance to an ti-CD8 or cyclosporine. Cytotoxic T cell precursor frequencies directe d against the mismatched donor HLA class I antigens were similar in no nrejectors and rejectors. However, rejection was strongly associated w ith the presence of primed, donor-specific CTL, whereas these primed c ells were absent in case of good graft function. These data show that HLA antigens of a transplanted cornea are immunogenic and targets for rejection by cytotoxic T cells. Therefore, this study supports the nee d for HLA-A and -B matching in corneal transplantation in patients wit h a high probability of rejection.