Du X X, Guo Y L, Zhao Y P, Yang M, Chang S, Liu B, Cai L J, Chen Z K
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, and Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Transplant Proc. 2018 Dec;50(10):3314-3320. doi: 10.1016/j.transproceed.2018.04.043. Epub 2018 Apr 18.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells that suppress immune responses during organ transplantation and participate in mediating long-term graft survival and immune tolerance in animal transplant models. However, their role in regulating transplant tolerance in human subjects is not well understood. In the present study, we investigated the role of MDSCs in mediating long-term graft survival in almost-tolerant kidney transplant recipients (ATKTRs) and the mechanism(s) responsible for increasing MDSC numbers in these recipients.
Peripheral blood mononuclear cells (PBMCs) from whole blood samples were collected from 30 ATKTRs (graft survival, > 10 years after kidney transplant [KTx]) treated with low doses of immunosuppressive drugs and with stable kidney function, 10 short-term graft survival kidney transplant recipients (STKTRs; graft survival, ∼1-3 years post-KTx) with stable kidney function, and 10 healthy donors (HDs). MDSC and regulatory T cell (Tregs) levels were analyzed using multicolor flow cytometry in PBMCs.
ATKTRs had significantly higher levels of monocytic MDSCs (P < .001) and CD4CD25FoxP3 Tregs than STKTRs and HDs. Furthermore, the M-MDSC levels correlated positively with the survival rates, estimated glomerular filtration rates (eGFRs) of grafts, and the levels of CD4CD25FoxP3 Tregs in ATKTRs.
Accumulation of high levels of MDSCs was observed in ATKTRs. Changes in MDSC levels may play important roles in mediating transplant tolerance and regulating Tregs. Therefore, we propose that MDSCs may be potentially used for recognizing tolerant transplant recipients and guiding dosage reduction for immunosuppressive drugs for KTx.
髓系来源的抑制细胞（MDSCs）是一类异质性的未成熟细胞群体，在器官移植过程中可抑制免疫反应，并参与介导动物移植模型中的长期移植物存活及免疫耐受。然而，它们在调节人类受试者移植耐受中的作用尚不清楚。在本研究中，我们调查了MDSCs在介导几乎耐受的肾移植受者（ATKTRs）长期移植物存活中的作用，以及导致这些受者中MDSC数量增加的机制。
从30例接受低剂量免疫抑制药物治疗且肾功能稳定的ATKTRs（肾移植[KTx]后移植物存活>10年）、10例肾功能稳定的短期移植物存活肾移植受者（STKTRs；KTx后移植物存活约1 - 3年）以及10例健康供者（HDs）的全血样本中收集外周血单核细胞（PBMCs）。使用多色流式细胞术分析PBMCs中的MDSC和调节性T细胞（Tregs）水平。
ATKTRs的单核细胞MDSCs（P <.001）和CD4CD25FoxP3 Tregs水平显著高于STKTRs和HDs。此外，ATKTRs中的M - MDSC水平与移植物存活率、估计肾小球滤过率（eGFRs）以及CD4CD25FoxP3 Tregs水平呈正相关。
在ATKTRs中观察到高水平MDSCs的积累。MDSC水平的变化可能在介导移植耐受和调节Tregs中起重要作用。因此，我们提出MDSCs可能潜在地用于识别耐受的移植受者，并指导肾移植免疫抑制药物的减量。
