Thomson Angus W, Zahorchak Alan F, Ezzelarab Mohamed B, Butterfield Lisa H, Lakkis Fadi G, Metes Diana M
Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine , Pittsburgh, PA , USA.
Front Immunol. 2016 Jan 28;7:15. doi: 10.3389/fimmu.2016.00015. eCollection 2016.
Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.
树突状细胞（DC）是一种罕见的专职抗原呈递细胞，具有诱导或调节同种免疫反应的能力。在多种条件下可在体外生成具有下调器官移植中发生的急性和慢性炎症状态潜力的调节性DC（DCreg）。在此，我们提供了在临床器官移植中评估DCreg疗法的理论依据，目的是促进持续的、供体特异性低反应性，同时降低排斥反应的发生率和严重程度，并减少患者对抗排斥药物的依赖。在啮齿动物或非人灵长类动物中，生成抑制T细胞反应并延长移植存活时间的供体或受体来源的DCreg已得到充分描述。最近，我们机构已生产出符合药品生产质量管理规范（GMP）级别的DCreg，用于人类器官移植的前瞻性研究。我们简要回顾了器官移植中调节性免疫治疗的经验，并描述了我们生成和鉴定人单核细胞来源的DCreg的经验。我们提出了一项I/II期安全性研究，其中将详细研究供体来源的DCreg与传统免疫抑制相结合对亚临床和临床排斥反应以及宿主同种免疫反应的影响。
