STUDIES OF THE MECHANISM OF TOLERANCE INDUCED BY SHORT-TERM IMMUNOSUPPRESSION WITH CYCLOSPORINE IN HIGH-RISK CORNEAL ALLOGRAFT RECIPIENTS

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Abstract
Transplantation of unmatched allogeneic corneas into highly vascularized recipient eyes under the cover of short-term immunosuppression with cyclosporine enables permanent engraftment (2). The aim of this study was to further elucidate the mechanism(s) underlying this tolerant state. In eight “high-risk” cornea recipients the clone sizes of donor-specific and third-party reactive cytotoxic T cell precursors were assessed by limiting dilution analyses before and at three and six months after transplantation. Acquired allograft tolerance in these patients was not accompanied byclonal reduction of donor-specific CTL-p, whereas in the case of an irreversible rejection the donor-specific CTL pool size was significantly enlarged. This donor-specific CTL-p in crease could already be seen two months before clinical manifestation. These patterns differed from that of tolerant renal transplant patients, in whom marked and donor-specific reduction of CTL-p was observed (2). During rejection identical patterns with increasing do nor-specific CTL-p frequencies were seen in both groups of patients. We conclude that induction of tolerance by short-term CsA to unmatched cornea grafts is not caused by clonal reduction of the effector precursor cell pool.