CELL-MEDIATED CYTOTOXICITY TOWARD THE DONOR IN PATIENTS WITH WELL-FUNCTIONING KIDNEY GRAFTS

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Abstract
Patients with well-functioning kidney allografts from 1-HLA-haplotype-mismatched related donors have strongly reduced donor-specific cell-mediated cytotoxicity 2-10 yr after receiving their grafts. This could also be demonstrated in secondary in vitro cell-mediated lympholysis (CML). Even though secondary donor-specific CML did not exceed 10% at an effector-to-target cell ratio of 50:1, specific lysis of donor target cells increased significantly with increasing effector cell concentrations. The weak cytotoxicity toward the donor could be enhanced neither through pool-cell stimulation nor by adding exogenous interleukin 2 (IL-2) during the induction phase. Growth factors were produced in the cultures during the induction of cytotoxic cells in concentrations comparable to those of the sibling control. No evidence was obtained that lack of IL-2 was causing the decreased cytotoxicity in these patients. In vivo depletion of cytotoxic cells with high lytic efficiency may be the reason for the strongly reduced donor-specific cytotoxicity.