Analysis of Rejection Mechanism and Indutcion of Unresponsiveness in Organ Transplantation

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It is well known that the major histocompatibility complex (MHC) plays an important role as to whether a graft is accepted or rejected. In the present study, rat renal allografting was performed to investigate the most effective methods that induce immunological unresponsiveness.1. Rejection modelTO (RT1^u), LEW (RT1^l), F344 (RT1^<lv>) rats were used as donors, and WKAH (RT1^k) rats as recipients. All these grafts were rejected within 16 days.2. Experiments for prolongation of allograft survival(1) Anti-Ia monoclonal antibody : The donor (F344) kidney was perfused with 1mg of anti-F344-Ia antibody (4B4) before transplantation, then the perfused graft was transplanted to WKAH rats (perfusion group). To make another experiment, we administered anti-recipient-Ia antibody (1E4) intravenously to WKAH rat after the perfused kidney was transplanted (perfusion^+iv group). Mean survival time of these 2 group prolonged significantly. However, there was no significant long suvivor.(2) Preimmunza … More tion with donor strain spleen cells : The recipient rat (WKAH) was preimmunized with 5x10^7 donor strain (TO) spleen cells 1 week prior to transplantation. Six of 8 preimmunized rat survived more than 192 days.(3) Short term administration of 15-deoxyspergualin (DSG) : TO rat kidney was transplanted to WKAH rat. In DSG group, 5mg/kg/day DSG was administered intramuscularily for 4 days from the 4th postoperative day. The short term administration (only 4 days) of DSG induced indefinite allograft survival.3. Analysis of mechanisms of long term survivingAfter renal allografting was performed from TO to preimmunized WKAH rats, recipients sera suppressed MLR nonspecifically for 2 weeks after grafting, but had no suppressive effect after 4 weeks. OX 8 positive cells continuously suppressed MLR specifically in donor type cells. In the DSG group, WKAH rat accepted TO skin graft, but rejected the skin grafts from other strain. These data indicated that the unresponsiveness induced by DSG was donor specific. Less