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Purpose : Donor specific immune tolerance is thought to be the ideal state for the recipient after organ transplantation. The administration of donor antigens and cyclophosphamide has been reported to... induce donor specific immune tolerance in heart or liver transplantation. However, the effectiveness of this method for small bowel transplantation has not yet been studied. We assessed the cyclophosphamide induced immune tolerance on rat fetal small bowel transplantation. Methods : Lewis rats (RT1l, n=99) were used as recipients while either F344 (RT1l, n= 44) or WKAM (RT1u, n=47) rats were used as donors. The combination of F344 and Lewis rats produces an immunologically low responder, while that of WKAM and Lewis rat produces a high responder. Bone marrow and spleen cells were harvested from the donor rats and 3x108/kg of each were administrated to the recipient rats intravenously on day 0. Next, cyclophosphamide was given either divisionally or bolously. The fetal small bowel of the same strain as the donor was transplanted into the rectus muscle of the recipient abdominal wall on day 10. On day 17, all grafts were taken out and graft survival was thereafter evaluated. The body weight of recipient was also assessed. Results : Most of the grafts (87.5 %) survived in the F344-Lewis rat (low responder) combination using the divisional administration of 120 mg/kg of cyclophosphamide. Histologically, most of them showed the whole layers of the intestinal architectureto be well preserved. The weight loss of the recipient was minimal after divisional administration. In contrast, no graft survived in the WKAM-Lewis rat (high responder) combination. Conclusions : Immune tolerance is considered to be induced by the administration of donor specific antigen and cyclophosphamide in an immunologically low responder combination. Therefore, this method is expected to be useful as an adjuvant therapy and may also be able to reduce the dose of immunosuppressive agents in living-related clinical small intestinal transplantation.
背景/目的:ドナー特異的免疫寛容は臓器移植において理想的な状態と考えられる.ドナー抗原とサイクロフォスファミド投与による免疫寛容誘導はいままで心移植や肝移植では報告がみられるが,小腸移植における有用性は全く報告がない.我々はラット胎児を用いた小腸移植モデルにおいてサイクロフォスファミド投与による免疫寛容誘導を検討した.方法:ルイスラット(RT11,n=99)をレシピエント,F344(RTll,n=44)またはWKAM(RTlu,n=47)をドナーとした.F344からルイスラットへの移植は弱免疫反応群として,WKAMからルイスラットへの移植は強免疫反応群として用いた.ドナーから骨髄および脾細胞を採取しそれぞれ3x108/kgずつレシピエントへ第0日に静脈投与した.次ぎにサイクロフォスファミドを分割または一括投与した.第10日にドナーと同じストレインのラットの胎仔の小腸を採取し,レシピエントの腹直筋内へ移植した.第17日にグラフトを摘出し生着を判定した.レシピエントの体重変化も評価した.結果:弱免疫反応群のサイクロフォスファミド120mg/kgの分割投与群では大部分のグラフトが生着した.この群では組織学的に腸管の全層構造が維持されていた.体重減少も分割投与群が一括投与群よりも少なかった.一方,強免疫反応群ではグラフト生着は全くみられなかった.結論:ドナー抗原とサイクロフォスファミド投与による免疫寛容誘導はラット小腸移植において,強免疫反応群では得られないが,弱免疫反応群では得られると考えられる.したがってこの方法は臨床の生体間小腸移植では免疫抑制剤の量を減らせる補助療法としての有用性が期待できる.続きを見る
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Mendeley出力
fam96_2_p049