Ethylene carbodiimide-fixed donor splenocytes combined with alpha-1 antitrypsin induce indefinite donor-specific protection to mice cardiac allografts
Ethylene carbodiimide-fixed donor splenocytes combined with alpha-1 antitrypsin induce indefinite donor-specific protection to mice cardiac allografts
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乙烯碳二亚胺固定供体脾细胞与α-1抗胰蛋白酶联合诱导对小鼠心脏同种异体移植物的无限期供体特异性保护
DOI：
10.1111/tri.12903
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发表时间：
2017
影响因子：
3.1
通讯作者：
Chen Guodong
中科院分区：
文献类型：
--
作者：
Lai Xingqiang;Qiu Longhui;Zhao Yi;Yu Shuangjin;Wang Chang;Zhang Jin;Ning Fen;Chen Lizhong;Chen Guodong
移植物周围输注乙烯碳二亚胺固定的供体脾细胞（ECDI-SP）可诱导胰岛和心脏同种异体移植物的保护作用。然而，移植围术期促炎细胞因子的产生可能会抵消ECDI‐ SP的作用。因此，我们假设阻断促炎细胞因子分泌，同时增加抗炎细胞因子水平将增强ECDI‐ SP的耐受诱导疗效。本研究的目的是确定使用ECDI‐ SP联合短期α1‐抗胰蛋白酶（AAT）诱导耐受的有效性。使用小鼠心脏移植模型，我们证明了ECDI-SP + AAT以供体特异性方式有效地诱导了无限期的小鼠心脏同种异体移植物保护。这种作用伴随着通过降低促炎细胞因子（包括IFN-γ、TNF-α、IL-1β、IL-6、IL-17和IL-23）水平和增加抗炎细胞因子（包括IL-10、IL-13和TGF-β）水平来调节细胞因子，以及抑制效应T细胞（Teff）和扩增调节性T细胞（Teff）。因此，我们得出结论，组合的ECDI-SP和AAT似乎调节细胞因子的表达并调节Teff：Treg平衡，从而为移植物保护创造支持环境。我们将ECDI‐ SP和AAT结合的策略为诱导供体特异性移植耐受提供了一种有希望的方法。
Peritransplant infusion of ethylene carbodiimide‐fixed donor splenocytes (ECDI‐SPs) induces protection of islet and cardiac allografts. However, pro‐inflammatory cytokine production during the peritransplantation period may negate the effect of ECDI‐SPs. Therefore, we hypothesized that blocking pro‐inflammatory cytokine secretion while increasing levels of anti‐inflammatory cytokines would enhance the tolerance‐induced efficacy of ECDI‐SPs. The objective of this study was to determine the effectiveness of using ECDI‐SPs combined with a short course of α1‐antitrypsin (AAT) for induction of tolerance. Using a mice cardiac transplant model, we demonstrated that ECDI‐SPs + AAT effectively induced indefinite mice cardiac allograft protection in a donor‐specific fashion. This effect was accompanied by modulation of cytokines through decreasing levels of pro‐inflammatory cytokines (including IFN‐γ, TNF‐α, IL‐1β, IL‐6, IL‐17, and IL‐23) and increasing levels of anti‐inflammatory cytokines (including IL‐10, IL‐13, and TGF‐β), and by inhibition of effector T cells (Teff) and expansion of regulatory T cells (Tregs). Therefore, we concluded that combined ECDI‐SPs and AAT appeared to modulate the expression of cytokines and regulate the Teff:Treg balance to create a support milieu for graft protection. Our strategy of combining ECDI‐SPs and AAT provides a promising approach for inducing donor‐specific transplant tolerance.