Aberrant T cell responses in the bone marrow microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation.
Aberrant T cell responses in the bone marrow microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation.
复制标题
异基因造血干细胞移植后移植功能不良患者骨髓微环境异常T细胞反应
DOI：
10.1186/s12967-017-1159-y
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发表时间：
2017-03-14
影响因子：
7.4
通讯作者：
Huang XJ
中科院分区：
文献类型：
--
作者：
Kong Y;Wang YT;Cao XN;Song Y;Chen YH;Sun YQ;Wang Y;Zhang XH;Xu LP;Huang XJ
移植物功能低下是异基因造血干细胞移植（allo-HSCT）后危及生命的并发症。然而，骨髓免疫微环境中T细胞亚群的异常，包括Th 17、Tc 17、Th 1、Tc 1、Th 2、Tc 2细胞和调节性T细胞（Treg），是否参与PGF的发病机制尚不清楚。这项前瞻性巢式病例对照研究纳入了20例PGF患者，40例allo-HSCT后移植物功能良好（GGF）的匹配患者和20例健康供体（HD）。流式细胞仪检测Th 17、Tc 17、Th 1、Tc 1、Th 2、Tc 2细胞、Tc 17及其亚群。产生IL-17的刺激的CD 4+和CD 8 + T细胞的比例显著较高在PGF患者的BM中发现Th 17和Tc 17的百分比高于GGF患者和HD的BM，而在PGF患者中Tc 17的百分比与GGF患者和HD中的那些相当，导致PGF患者的BM中Th 17细胞/Th细胞的比率相对于GGF患者的BM中Th 17细胞/Th细胞的比率显著升高。此外，在PGF患者的BM中，CD 4+和CD 8 + T细胞均朝向1型免疫应答极化。本研究揭示骨髓免疫微环境中异常的T细胞反应可能参与allo-HSCT后PGF的发病机制。这些发现将有助于优化免疫调节策略，改善移植后PGF患者的预后。本文的在线版本（doi：10.1186/s12967-017-1159-y）包含补充材料，可供授权用户使用。
Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear. This prospective nested case–control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD). Th17, Tc17, Th1, Tc1, Th2, Tc2 cells, Tregs and their subsets were analyzed by flow cytometry. A significantly higher proportion of stimulated CD4+ and CD8+ T cells that produced IL-17 (Th17 and Tc17) was found in the BM of PGF patients than in the BM of GGF patients and HD, whereas the percentages of Tregs in PGF patients were comparable to those in GGF patients and HD, resulting in a dramatically elevated ratio of Th17 cells/Tregs in the BM of PGF patients relative to those in GGF patients. Moreover, both CD4+ and CD8+ T cells were polarized towards a type 1 immune response in the BM of PGF patients. The present study revealed that aberrant T cell responses in the BM immune microenvironment may be involved in the pathogenesis of PGF after allo-HSCT. These findings will facilitate the optimization of immune regulation strategies and improve the outcome of PGF patients post-allotransplant. The online version of this article (doi:10.1186/s12967-017-1159-y) contains supplementary material, which is available to authorized users.