Morelli Adrian E, Thomson Angus W
aDepartment of Surgery, Starzl Transplantation Institute bDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Curr Opin Organ Transplant. 2014 Aug;19(4):348-56. doi: 10.1097/MOT.0000000000000097.
Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCregs) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCregs (donor or recipient) and their mode of action, in-situ targeting of DCregs, and optimal therapeutic regimens to promote DCreg function.
Recent studies have defined protocols and mechanisms whereby ex-vivo-generated DCregs of donor or recipient origin subvert allogeneic T-cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen is acquired, processed and presented by autologous dendritic cells, on the stability of DCregs, and on in-situ targeting of dendritic cells to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCregs in a clinically relevant nonhuman primate organ transplant model and production of clinical grade DCregs support early evaluation of DCreg therapy in human graft recipients.
We discuss strategies currently used to promote dendritic cell tolerogenicity, including DCreg therapy and in-situ targeting of dendritic cells, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application.
在过去二十年中，对小鼠移植模型进行的广泛研究令人信服地证明了调节性树突状细胞（DCregs）促进同种异体移植物长期存活的能力。我们回顾了有关治疗性DCregs来源（供体或受体）及其作用方式、DCregs的原位靶向以及促进DCreg功能的最佳治疗方案的重要考虑因素。
最近的研究已经确定了方案和机制，通过这些方案和机制，来自供体或受体来源的体外生成的DCregs能够颠覆同种异体T细胞反应并促进长期器官移植存活。特别令人感兴趣的是自体树突状细胞如何获取、处理和呈递供体抗原，DCregs的稳定性，以及树突状细胞的原位靶向以促进其致耐受性功能。DCregs在临床相关的非人灵长类动物器官移植模型中的治疗效果以及临床级DCregs的产生的新证据支持了在人类移植受者中对DCreg治疗进行早期评估。
我们讨论了目前用于促进树突状细胞致耐受性的策略，包括DCreg治疗和树突状细胞的原位靶向，以期更好地理解潜在机制并确定最有前景的治疗应用策略。
