The inhibitory effect of FK506 on cytotoxic T-lymphocyte killing

The immunosuppressant FK506 inhibits N-alpha-benzyloxylcarbonyl-L-lysine thiobenzyl ester (BLT) esterase release from cytotoxic T lymphocytes (CTL). In addition, serine esterase has been demonstrated to be strongly associated with CTL killing. In the present study, the effect of FK506 on the activity of CTL killing against target cells was examined. FK506 inhibited lysis of antigen (Ag)-treated CTL target cells by auto-CTL, but failed to inhibit lysis of conventional P815 target cells by CTL. Moreover, FK506 inhibited DNA fragmentation of CTL target cells lysed by auto-CTL. Killing of CTL target cells by FK506-pretreated auto-CTL was inhibited, but FK506-pretreated CTL target cells were killed by auto-CTL. Incubation of both FK506 and Ag-pretreated CTL target cells with untreated auto-CTL induced DNA fragmentation. These indicated that FK506 inhibited CTL killing by influencing effector, but not CTL target cells. These results suggest that FK506 may function by inhibiting alloreactive CTL killing in organ transplantation in addition to the interruption of the T-cell receptor signal transduction leading to cytokine production.