Costimulation blockade followed by a 12-week period of cyclosporine A facilitates prolonged drug-free survival of rhesus monkey kidney allografts
Costimulation blockade followed by a 12-week period of cyclosporine A facilitates prolonged drug-free survival of rhesus monkey kidney allografts
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DOI：
10.1097/01.tp.0000158426.64631.ed
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发表时间：
2005-06-15
期刊：
影响因子：
6.2
通讯作者：
Jonker, M
中科院分区：
文献类型：
--
作者：
Haanstra, KG;Sick, EA;Jonker, M
共刺激阻断作为单一的免疫抑制治疗方式不足以预防移植物排斥反应。在这里，我们报道了一种使用抗CD40和CD86的拮抗抗体的诱导治疗，从第1天到第56天每周给药两次，然后在恒河猴异基因肾移植模型上延迟12周的小剂量环孢素A(CsA)治疗。小剂量CsA治疗从第42天开始，逐渐减少，直到第126天完全停止治疗。单独使用抗CD40/86抗体治疗后移植物存活时间分别为61、71、75、78和116天。共刺激阻断后CsA使四只动物中的两只获得了超过3年的无药生存。没有一只动物产生供体特异性同种异体抗体。转化生长因子-β产生细胞在早期和晚期肾移植活检中都存在，并可能在观察到的无药物移植肾的长期存活中发挥作用。
Costimulation blockade as a single immunosuppressive treatment modality is not sufficient to prevent graft rejection. Here, we report an induction therapy using antagonistic antibodies against CD40 and CD86, given twice weekly from day-1 until day 56, followed by a delayed 12-week course of low-dose cyclosporine A (CsA) treatment in the rhesus monkey kidney-allo graft model. Low-dose CsA treatment was initiated on day 42 and tapered until total cessation of all treatment on day 126. Treatment with anti-CD40/86 alone resulted in graft survival of 61, 71, 75, 78, and 116 days. Costimulation blockade followed by CsA resulted in more than 3-year drug-free survival in two of four animals. None of the animals developed donor-specific alloantibodies. Transforming growth factor-beta producing cells are present in early as well as in late kidney-graft biopsies and could play a role in the observed long-term drug-free graft survival.