Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates.
Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates.
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调节性树突状细胞输注延长非人类灵长类动物的肾脏同种异体移植存活。
DOI：
10.1111/ajt.12310
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Thomson AW
中科院分区：
文献类型：
--
作者：
Ezzelarab MB;Zahorchak AF;Lu L;Morelli AE;Chalasani G;Demetris AJ;Lakkis FG;Wijkstrom M;Murase N;Humar A;Shapiro R;Cooper DK;Thomson AW
我们研究了调节性树突状细胞（DCreg）的影响，从维生素D3和IL-10中的精氨酸动员的供体血液单核细胞，对肾移植存活在临床相关的恒河猴模型。DCreg表达低MHC II类和共刺激分子，但相对高水平的程序性死亡配体-1（B7-H1），并对促炎性精氨酸诱导的成熟具有抗性。肾移植前7天静脉输注B7-CD 28共刺激阻断剂CTLA 4 Ig（3.5 ~ 10×106/kg）。CTLA 4 Ig给药长达8周，雷帕霉素从第-2天开始，维持血药浓度逐渐降低，直到6个月时完全停药。对照猴（无DC输注; n= 6）的移植物存活时间中位数为39.5天，DCreg治疗的动物（n=6）为113.5天（p< 0.05）。没有与DCreg输注相关的不良事件，也没有基于循环供体特异性同种抗体水平诱导宿主致敏的证据。免疫学监测还显示，与对照组相比，DCreg治疗的猴子中供体反应性记忆CD 95 + T细胞的调节和记忆/调节T细胞比率的降低。移植物组织学显示两组均出现中度T细胞和Ab介导的排斥反应。这些发现证明了进一步临床前评估DCreg疗法及其在器官移植中的治疗潜力。
We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on day −2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n=6) and 113.5 days (p< 0.05) in DCreg-treated animals (n=6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95+ T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further pre-clinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation.
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影响因子：
4.4
作者：
Kenna, Tony J.;Waldie, Tanya;Steptoe, Raymond J.
通讯作者：
Steptoe, Raymond J.
影响因子：
20.3
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影响因子：
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作者：
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通讯作者：
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8.8
作者：
Charbonnier, L. -M.;Vokaer, B.;Le Moine, A.
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