Induced immune destruction of long-surviving, H-2 incompatible kidney transplants in mice.

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Abstract
Various modes for producing the specific immune destruction of surviving kidney transplants between mice were tested. Kidney transplants among mice which were incompatible at the H-2 locus but which were surviving in excellent condition for several weeks without immunosuppression were utilized. When immune damage to these surviving organs resulted from the treatments being tested it was readily detectable by changes in the blood urea N levels of their recipients. The treatments included means of heightening immune reactivity to donor antigens passively by the transfer of either specifically activated cells, immune serum or by the active generation of increased responsiveness. Infusions of an antiserum specifically reactive with the histocompatibility antigens of the transplant were ineffective in causing damage to the kidney unless exogenous complement, in the form of rabbit serum absorbed with mouse tissue, was also given. The injection of lymph node and spleen cells from recipient strain mice which were highly immunized to donor antigens caused definite but transient damage to transplanted kidneys. Stimulation of recipient responsiveness by additional donor tissue antigens presented as skin grafts was ineffective although i.v. injections of lymphoid cells provoked an evanescent reaction. Combining donor strain lymphoid cell treatment with a prior injection of cyclophosphamide (4 mg, 2 days before cell injection) and/or treatment with BCG (2 .times. 107 organisms, 22 days before cell injection) caused an intense and specific immune response to donor antigens with rapid onset of transplant damage. The maximal effect observed followed the combined use of all 3 agents in which case every transplant was fully rejected by 7-8 days after donor cell injection. An otherwise stable balance between an incompatible transplanted organ and its host can be decisively upset by treatments which provoke a heightened, specific immune response. The conferral of immunity passively by transferring serum or lymphoid cells from sensitized donors was much less successful in causing damage to transplants. The maturation of full competent killer T [thymus-derived] cells is retarded in long-term kidney transplant recipients and there was no direct evidence of suppressor cell activity in them. The fact that only transient damage to transplants occurred even after the transfer of large numbers of immunized lymphoid cells prevents the dismissal of the participation of an active suppressor mechanism.