1 Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA. 2 Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA. 3 Address correspondence to: Angus W. Thomson, Ph.D., D.Sc., Departments of Surgery and Immunology, University of Pittsburgh School of Medicine, Thomas E. Starzl Transplantation Institute, 200 Lothrop Street, Biomedical Science Tower W1540, Pittsburgh, PA 15213.
Transplantation. 2014 Feb 27;97(4):367-79. doi: 10.1097/TP.0b013e3182a860de.
Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages, regulatory dendritic cells, and myeloid-derived suppressor cells to regulate alloimmunity, their potential as cellular therapeutic agents, and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity after RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and to promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and to usher in a new era of immune modulation exploiting cells of myeloid origin.
调节性髓系细胞（RMC）作为免疫抑制（IS）药物的新型靶点，作为细胞治疗药物具有很大的潜力。本文讨论了调节性巨噬细胞、调节性树突状细胞和髓源性抑制细胞调节同种异体免疫的能力、它们作为细胞治疗药物的潜力以及靶向其功能的 IS 药物。我们考虑了生成 RMC 的方案以及用于过继细胞治疗的供体或受体来源细胞的选择。此外，还讨论了 RMC 转移后细胞迁移和抗原（Ag）特异性的问题。对这些细胞的免疫生物学的深入了解增加了将 RMC 推向临床以减轻当前 IS 药物负担和促进 Ag 特异性耐受的可能性。在本综述的后半部分，我们讨论了已建立的和实验性 IS 药物对髓系细胞群的影响。历史上被认为主要作用于 T 细胞激活和增殖的 IS 药物，现已成为 RMC 功能的重要调节剂。更好地了解 IS 药物对 RMC 的影响将增强我们开发细胞治疗方案以促进这些细胞功能的能力。此外，新型 IS 药物可能被设计用于在原位靶向 RMC，以促进移植中的 Ag 特异性免疫调节，并开创利用髓系细胞进行免疫调节的新时代。
