The presence of activated donor HLA class I-reactive T lymphocytes is associated with rejection of corneal grafts.

Abstract

Although the cornea is considered to be an immunological privileged site, corneal transplantation can result in immunological rejection followed by graft failure, especially in patients with vascularized corneas. Several studies suggest a beneficial effect of matching for the HLA class I antigens on corneal graft survival, although a large study (the 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 problem in another way. A more direct way to assess the importance of HLA class I antigens in corneal transplantation is to measure whether rejection of an allograft is associated with priming of cytotoxic T lymphocytes recognizing the mismatched HLA antigens of the donor. In the present study, 13 patients with good graft function and 10 with ongoing rejection of their corneal allografts were analyzed for the presence of CTL directed against mismatched donor HLA class I antigens, by limiting dilution assays. CTLs were divided into naive and primed CTLs based on the measurement of their in vitro sensitivity or resistance to anti-CD8 or cyclosporine. Cytotoxic T cell precursor frequencies directed against the mismatched donor HLA class I antigens were similar in nonrejectors and rejectors. However, rejection was strongly associated with the presence of primed, donor-specific CTL, whereas these primed cells 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 need for HLA-A and -B matching in corneal transplantation in patients with a high probability of rejection.