Enforcement of specific unresponsiveness by the long-term presence of allogeneic heart grafts.

Mechanisms underlying the maintenance of long-term heart allografts were analyzed in rats treated with Cyclosporine. It was shown that acceptance of allografts after cyclosporine did not involve the attenuation of immunogenicity of the grafts. This conclusion was drawn from two observations: (1) Pretreatment of the donors with cyclosporine did not cause prolongation of graft survival time; and (2) cyclosporine stabilized allografts were normally rejected by secondary recipients when retransplanted on day 30. Studies of the acceptance of skin grafts from the heart donor strain indicated the existence of a mechanism to maintain donor-specific unresponsiveness in the presence of a stable allograft in a time-dependent manner. Thus, the mean rejection time of F344 skin grafts on WKA rats bearing F344 hearts was more than 80 days when transplanted on day 210, but it was 32 days when they were transplanted on day 30. Active participation of specific suppressor cells in the maintenance of unresponsiveness was suggested because data obtained in the cell transfer experiments was statistically significant. Transfer of lymphocytes from rats bearing long-term grafts showed a tendency to delay rejection of skin grafts by sublethally irradiated hosts, but it failed to delay the rapid rejection by normal lymphocytes cotransferred to the same recipients.