Song Yang, Shi Min-Min, Zhang Yuan-Yuan, Mo Xiao-Dong, Wang Yu, Zhang Xiao-Hui, Xu Lan-Ping, Huang Xiao-Jun, Kong Yuan
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, China.
Biol Blood Marrow Transplant. 2017 Jun;23(6):906-912. doi: 10.1016/j.bbmt.2017.02.021. Epub 2017 Mar 9.
Prolonged isolated thrombocytopenia (PT) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether abnormalities of the bone marrow (BM) immune microenvironment are involved in the pathogenesis of PT remains unknown, however. Twenty patients with PT, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD) were enrolled in this nested case-control study. Th1, Th2, Tc1, Tc2, Th17, and Treg cells were analyzed by flow cytometry, and IFN-γ, IL-4, IL-17, IL-6, IL-21, and thrombopoietin levels in BM plasma were evaluated with a cytometric bead assay and ELISA. Relative to GGF patients and HD controls, PT patients had significantly higher proportions of Th1 and Tc1 cells, resulting in higher Th1/Th2 and Tc1/Tc2 ratios in the BM microenvironment. In addition, the excessive polarization of Th17 was observed in patients with PT. Changes in BM plasma cytokines were consistent with our cellular findings. These results suggest that dysregulated T cell responses in the BM microenvironment might play an important role in the pathogenesis of PT.
长期孤立性血小板减少症（PT）是异基因造血干细胞移植（allo-HSCT）后的一种严重并发症。然而，骨髓（BM）免疫微环境异常是否参与PT的发病机制尚不清楚。本巢式病例对照研究纳入了20例PT患者、40例allo-HSCT后移植功能良好（GGF）的匹配患者以及20名健康供者（HD）。通过流式细胞术分析Th1、Th2、Tc1、Tc2、Th17和调节性T细胞（Treg），并采用细胞计数微球分析和酶联免疫吸附测定法评估BM血浆中干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）、白细胞介素-17（IL-17）、白细胞介素-6（IL-6）、白细胞介素-21和血小板生成素水平。相对于GGF患者和HD对照组，PT患者的Th1和Tc1细胞比例显著更高，导致BM微环境中Th1/Th2和Tc1/Tc2比值更高。此外，在PT患者中观察到Th17过度极化。BM血浆细胞因子的变化与我们的细胞研究结果一致。这些结果表明，BM微环境中T细胞反应失调可能在PT的发病机制中起重要作用。
