Effect of rabbit anti-human thymocyte globulin on lymphocyte subpopulations and functions following allotransplantation in the rhesus monkey.
The survival time of skin allografts from RhLA-nonidentical, unrelated donors was increased from a mean of 7.69 days in controls (n = 20) to a mean of 32.53 days in rhesus monkeys (n = 21) receiving a total dose of 250 mg of rabbit anti-human thymocyte globulin (RATG) per kg. Immunological monitoring studies were performed on the peripheral blood of mononuclear cells in control and treated monkeys. After administration of RATG, the percentage of E rosette-forming cells (E-RFC) was greater than 90% depressed, and the percentage of EAC rosette-forming cells was increased 5-fold in the circulation. Significant numbers of RATG-coated cells were detected only during the first week after RATG treatment. The percentage of E-RFC recovered to pretreatment levels within 3 to 4 weeks after RATG treatment, although the absolute E-RFC count remained depressed for 2 to 3 months. In addition, the in vitro proliferative responsiveness to polyclonal mitogens and to allogeneic lymphocytes remained greater than 80% depressed for 2 to 3 months after RATG treatment. The incidence of post-transplant-specific antidonor lymphocyte-mediated cytotoxicity (LMC) was similar in controls (85%) and RATG-treated monkeys (81%), and the appearance of LMC was correlated (r = 0.711) with partial recovery of absolute ERFC counts in the treated group. The appearance and peak of LMC were delayed (P less than 0.001) in RATG-treated monkeys, but preceded and correlated with rejection. Prior to rejection, the serum of RATG-treated monkeys inhibited LMC. Antibody-dependent cellular cytotoxicity appeared after rejection in the majority of recipients in both groups. The appearance and peak of antibody-dependent cell-mediated cytotoxicity (ADCC) were delayed (P less than than 0.001) in RATG-treated monkeys, but did not exhibit a significant correlation with the time of rejection.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D006084:Graft Rejection; D006085:Graft Survival; D000882:Haplorhini; D006801:Humans; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D011817:Rabbits; D012397:Rosette Formation; D012867:Skin / Q000473:pathology; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents