Myeloid-derived suppressor cells (MDSC) are a heterogenous population of immunosuppressive myeloid cells now considered important immune regulatory cells in diverse clinical conditions, including cancer, chronic inflammatory disorders and transplantation. In rodents, MDSC administration can inhibit graft-versus-host disease lethality and enhance organ or pancreatic islet allograft survival. There is also evidence, however, that under systemic inflammatory conditions, adoptively-transferred MDSC can rapidly lose their suppressive function. To our knowledge, there are no reports of autologous MDSC administration to either human or clinically-relevant non-human primate (NHP) transplant recipients. Monocytic (m) MDSC have been shown to be more potent suppressors of T cell responses than other subsets of MDSC. Following their characterization in rhesus macaques, we have conducted a preliminary analysis of the feasibility and preliminary efficacy of purified mMDSC infusion into MHC-mismatched rhesus kidney allograft recipients. The graft recipients were treated with rapamycin and the high affinity variant of the T cell co-stimulation blocking agent cytotoxic T lymphocyte antigen 4 Ig (Belatacept) that targets the B7-CD28 pathway. Graft survival and histology were not affected by infusions of autologous, leukapheresis product-derived mMDSC on days 7 and 14 post-transplant (cumulative totals of 3.19 and 1.98 × 10⁶ cells/kg in n = 2 recipients) compared with control monkeys that did not receive MDSC (n = 2). Sequential analyses of effector T cell populations revealed no differences between the groups. While these initial findings do not provide evidence of efficacy under the conditions adopted, further studies in NHP, designed to ascertain the appropriate mMDSC source and dose, timing and anti-inflammatory/immunosuppressive agent support are likely to prove instructive regarding the therapeutic potential of MDSC in organ transplantation.

骨髓源性抑制细胞（MDSC）是免疫抑制性骨髓细胞的异质群体，现在被认为是多种临床条件下重要的免疫调节细胞，包括癌症、慢性炎症性疾病和移植。在啮齿动物中，MDSC 给药可以抑制移植物抗宿主病的致死率并增强器官或胰岛同种异体移植物的存活率。然而，也有证据表明，在全身炎症条件下，过继转移的 MDSC 会迅速失去其抑制功能。据我们所知，尚无对人类或临床相关的非人灵长类动物 (NHP) 移植受者进行自体 MDSC 给药的报道。单核细胞 (m) MDSC 已被证明比其他 MDSC 亚群更有效地抑制 T 细胞反应。在对恒河猴进行表征后，我们对将纯化的 mMDSC 输注至 MHC 不匹配的恒河肾同种异体移植受体的可行性和初步功效进行了初步分析。移植受者接受雷帕霉素和针对 B7-CD28 途径的 T 细胞共刺激阻断剂细胞毒性 T 淋巴细胞抗原 4 Ig (Belatacept) 的高亲和力变体进行治疗。移植后第 7 天和第 14 天，输注自体白细胞分离产物衍生的 mMDSC 不会影响移植物存活和组织学（ n = 2 名受者的累计总数为 3.19 和 1.98 × 10 ^{6 个}细胞/kg）。未收到 MDSC (n = 2)。效应 T 细胞群的序贯分析显示各组之间没有差异。 虽然这些初步研究结果并未提供在所采用条件下有效的证据，但旨在确定适当的 mMDSC 来源和剂量、时间和抗炎/免疫抑制剂支持的 NHP 进一步研究可能对 MDSC 的治疗潜力具有指导意义在器官移植方面。