First, there is an important difference in the response to injections of globulin prepared from the serum of immunized as compared to nonimmunized horses. use of antilymphoid serum for the protection of whole organ homografts. The present study is a further evaluation of the importance of this kind of immunosuppressive therapy for the protection of whole organ homografts in dogs, as well as an account of its subsequent application in humans. Antiserums against the lymphoid tissue of both species were raised in horses, characterized for toxicity and antibody content, and rendered to globulin as fully described elsewhere (4). The test organs in the canine experiments CCK2R Ligand-Linker Conjugates 1 were the kidney and liver. The clinical patients had renal homotransplantation. METHODS Canine experiments One hundred and thirty-four mongrel dogs weighing 10 to 25 kilograms were immunized against hepatitis and distemper and used as homograft CCK2R Ligand-Linker Conjugates 1 recipients. Operations were performed under sodium pentobarbital anesthesia combined with the tranquilizer phencyclidine hydrochloride. Renal transplants were accomplished by transferring the donor kidney to the contralateral recipient iliac fossa, with anastomoses of the renal artery to the proximal end of the cut common iliac artery, the renal vein to the side of the common iliac vein, and the ureter to the bladder. Bilateral recipient nephrectomy was always carried out. Orthotopic hepatic transplants were performed as previously described (15). Before and after both kinds of homotransplantation, blood urea nitrogen, serum bilirubin, alkaline phosphatase, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, and Rabbit polyclonal to INSL3 complete hematologic studies were obtained at frequent intervals. The development of canine antibodies against horse serum was monitored by determination of precipitin titers (4). Animals which died after transplantation were autopsied and the tissues examined by light microscopy. In a number of experiments, biopsies were taken at varying intervals after transplantation and examined both with light and electron microscopy. Antilymphoid plasma The 3 kinds of antilymphoid agents were obtained from immunized horses as described previously (4). The first was unabsorbed antilymphoid plasma with a leukoagglutinin titer of 1 1:16. to 1 1:256. The dose of 1 1 to 4 milliliters per kilogram was given intraperitoneally every 1 to 3 days for 5 to 30 days before renal homotransplantation and by a similar schedule during the first 20 or 30 postoperative days. After this time, the intervals between injections were increased to 4 to 30 days or therapy was stopped. The plasma was toxic. Of 36 dogs entered into the experiment, 11 died before operation. Twelve of the remaining 25 definitive test animals CCK2R Ligand-Linker Conjugates 1 had thymectomy 7 to 20 days before institution of plasma therapy. Antilymphoid serum The second product tested was antilymphoid serum with a titer of 1 1:32 to 1 1:128. This was obtained from 4 of the same horses, but it was prepared from coagulated blood and partially absorbed against 10 per cent dog red cell pack. Six dogs received renal homotransplantation with a comparable intraperitoneal dose schedule as that described for plasma. In addition, 6 other animals received kidneys with intraperitoneal antiserum therapy starting on the day of transplantation. The same antilymphoid serum was given intraperitoneally to CCK2R Ligand-Linker Conjugates 1 9 recipients of orthotopic liver homografts, beginning 1 to 26 days before operation. One of the pretreated dogs received no further therapy after transplantation, but the others had additional postoperative injections. Antilymphoid globulin The third kind of antilymphoid agent tested was crude globulin which was precipitated from immune horse serum with ammonium sulfate after absorption of the serum with dog red cells, and in some instances with dog serum, kidney, and liver. Many of the batches used were concentrated by lyophilization. The leukoagglutinating titer of the reconstituted injectate was 1:512 to 1 1:1,024. The subcutaneous dose schedule was 0.2 to 0.5 milliliter per kilogram per day. The effectiveness of immunosuppression was evaluated both with renal and orthotopic liver homotransplantation. For 25 kidney transplantations pretreatment of 7 to 13 days was provided for 12, and therapy was begun on the day of operation in the other 13. In 4 of 9 dogs receiving liver grafts therapy was started on the day of transplantation, and the other 5 had 5 to 26 days of pretreatment. In the recipients of both kidney and liver homografts, therapy was stopped from 35 to 60 days after transplantation. Another 4 dogs received renal homotransplantation after pretreatment for 60 days. No postoperative therapy was given to these animals..