| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Oral administration can induce unresponsiveness to protein antigens. However, a number of trials using oral administration of alloantigens have failed to induce operational tolerance. I demonstrated that multiple oral deliveries of donor alloantigen induced modest prolongation of a single MHC mismatched cardiac allograft. When anti-CD4 monoclonal antibody (mAb) was administered before the first oral delivery, all grafts survived for over 100 days. Moreover, a single oral delivery of alloantigen plus anti- CD4 mAb induced indefinite survival of not only a single MHC mismatched but also fully allogeneic cardiac grafts. Orally delivered cells could not be detected in mice, suggesting that the indirect antigen recognition was involved. In fact, oral delivery of K^b molecule plus anit-CD4 mAb induced indefinite survival. Furthermore, oral delivery of K^b combined with anti-CD4 mAb induced survival of fully allogeneic cardiac grafts, suggesting that the linked suppression may be involved in the induction phase. Fina ly, Oral delivery of ovalbumine plus anti-CD4 mAb induced prolonged survival of grafts when the ovalbumine was injected orally again at the time of transplantation. These findings provide a lot of helpful evidences for clinical application of oral tolerance to alloantigen.
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