Specific recipient-donor unresponsiveness mediated by a suppressor cell system in human kidney allograft tolerance

The immunological responsiveness of a panel of 26 consecutive cadaver kidney allograft patients with good graft tolerance was studied against cells from the specific donor. Among these 26 patients, 11 underwent acute cellular rejection and were studied during the rejection episode. An additional eight transplant patients, who lost their graft as a result of cellular rejection, were nephrectomized and studied 6 months after their return to hemodialysis as the control group of patients "at equivalent risk." A low responsiveness against the specific donor was observed in cases of good graft tolerance, but was absent during rejection and in the control group. By using mixing experiments, cells from tolerant patients were able to actively and selectively suppress the response of their autologous pretransplant cells stimulated by the specific donor cells. These suppressor cells were effective only when added during the first 48 hr of the culture and could respond at a suppressor to responder cell ratio from 1:1 to 1:4. Finally, our observations indicate that allogeneic unresponsiveness between donor-recipient pairs may be associated with the presence of suppressor cells affecting the generation of helper T cells only in the specific situation, i.e., donor-recipient, and only in cases of good graft tolerance.