INDUCTION OF SPECIFIC TOLERANCE BY INTRATHYMIC INJECTION OF RECIPIENTMUSCLE-CELLS TRANSFECTED WITH DONOR CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX

Induction of tolerance to allogeneic MHC antigens has been a goal in t he field of transplantation because it would reduce or eliminate the n eed for generalized immunosuppression. Although encouraging results ha ve been obtained in experimental models by exposing recipient thymus t o donor cells before transplantation, donor cells are not typically av ailable at that time, and the donor antigens responsible for the effec t are poorly defined. In the present study, thymic tolerance was demon strated without using donor cells. Recipient thymus was injected befor e transplantation with autologous myoblasts and myotubes that were gen etically modified to express allogeneic donor-type MHC class I antigen . Donor-specific unresponsiveness was induced to a completely MHC-disp arate liver transplant and to a subsequent donor-type cardiac allograf t, but not a third-party allograft. In vitro, recipient CTL demonstrat ed a 10-fold reduction in killing of donor cells, but not of third-par ty cells. Our results demonstrate: (1) that recipient muscle cells can be genetically engineered to induce donor-specific unresponsiveness w hen given intrathymically, and (2) transfected recipient cells express ing only donor MHC class I antigen can induce tolerance to a fully all ogeneic donor.