FK506 inhibits human lymphocyte migration and the production of lymphocyte chemotactic factors in liver allograft recipients

The macroglide immunosuppressant FK506 is effective at preventing and reversing hepatic allograft rejection. The establishment of-graft rejection is dependent upon an influx of lymphocytes from the circulation into the graft in response to locally secreted chemotactic factors. Thus, inhibition of lymphocyte migration might be an additional mode of action of FK506 that could block lymphocyte recruitment to rejecting liver allografts, In the present study, we provide evidence to support this hypothesis because we have demonstrated, using in vitro migration assays, that FK506 can inhibit the migration of lymphocytes, including CD4+ and CD8+ T-cells, to structurally diverse chemotactic factors that are present during human liver allograft rejection. In addition, FK506 acts on lymphocytes in patients with graft rejection to inhibit migration and to block the secretion of chemotactic factors in vitro. Thus, FK506 might reverse established graft rejection by inhibiting lymphocyte recruitment to the graft in vivo.