Renal allograft rejection is prevented by adoptive transfer of anergic T cells in nonhuman primates
Renal allograft rejection is prevented by adoptive transfer of anergic T cells in nonhuman primates
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DOI：
10.1172/jci23743
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发表时间：
2005-07-01
影响因子：
15.9
通讯作者：
Okumura, K
中科院分区：
文献类型：
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作者：
Bashuda, H;Kimikawa, M;Okumura, K
据报道，离体产生的无反应性T细胞在体外和体内具有免疫抑制作用。在这里，我们在非人类灵长类动物中测试了这个概念。通过与供体同种异体抗原在抗CD 80/CD 86单克隆抗体存在下共培养，使同种异体反应性T细胞在体外失去反应性，然后通过肾同种异体移植物过继转移至恒河猴受体。在制备无反应性细胞期间，接受者用环磷酰胺和环孢素A进行短暂治疗。肾移植后13天，将无反应性T细胞转移到受体，之后不再给予免疫抑制剂。所有接受治疗的受者的无排斥存活时间延长，6只动物中有3只长期存活（研究结束时为410-880天）。在长期存活的受者中，对同种异体抗原的增殖反应以供体特异性的方式被抑制，并且供体类型的皮肤同种异体移植物也被接受，但不接受第三方皮肤同种异体移植物，这表明已经诱导了抗原特异性耐受。我们的结论是，在非人灵长类动物中，通过阻断CD 28/B7共刺激产生的无反应性T细胞可以抑制过继移植后的肾移植排斥反应。这一策略可能适用于人体安全临床试验的设计。
Anergic T cells generated ex vivo are reported to have immunosuppressive effects in vitro and in vivo. Here, we tested this concept in nonhuman primates. Alloreactive T cells were rendered anergic ex vivo by coculture with donor alloantigen in the presence of anti-CD80/CD86 mAbs before adoptive transfer via renal allograft to rhesus monkey recipients. The recipients were briefly treated with cyclophosphamide and cyclosporine A during the preparation of the anergic cells. Thirteen days after renal transplantation, the anergic T cells were transferred to the recipient, after which no further immunosuppressive agents were administered. Rejection-free survival was prolonged in all treated recipients, and 3 of 6 animals survived long term (410-880 days at study's end). In the long-surviving recipients, proliferative responses against alloantigen were inhibited in a donor-specific manner, and donor-type, but not third-party skin allografts were also accepted, which demonstrated that antigen-specific tolerance had been induced. We conclude that anergic T cells generated ex vivo by blocking CD28/B7 costimulation can suppress renal allograft rejection after adoptive transfer in nonhuman primates. This strategy may be applicable to the design of safe clinical trials in humans.