Recruitment of CD8(+) T cells into bone marrow might explain the suppression of megakaryocyte apoptosis through high expression of CX3CR1(+) in prolonged isolated thrombocytopenia after allogeneic hematopoietic stem cell transplantation
Recruitment of CD8(+) T cells into bone marrow might explain the suppression of megakaryocyte apoptosis through high expression of CX3CR1(+) in prolonged isolated thrombocytopenia after allogeneic hematopoietic stem cell transplantation
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CD8( ) T 细胞募集到骨髓中可能解释异基因造血干细胞移植后长期孤立性血小板减少症中 CX3CR1( ) 高表达对巨核细胞凋亡的抑制
DOI：
10.1007/s00277-015-2436-6
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发表时间：
2015
影响因子：
3.5
通讯作者：
Zhang XH
中科院分区：
文献类型：
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作者：
Zhang Xiao-Hui;Wang Guo-Xiang;Zhu Hong-Hu;Liu Yan-Rong;Xu Lan-Ping;Han Wei;Chen Huan;Chen Yu-Hong;Wang Feng-Rong;Wang Jing-Zhi;Wang Yu;Zhao Ting;Chen Yao;Feng Ru;Fu Hai-Xia;Wang Min;Zhou Yi;Lv Meng;Liu Kai-Yan;Huang Xiao-Jun;Zhang XH
持续孤立性血小板减少症是异基因造血干细胞移植（allo-HSCT）后常见的并发症，与不良预后相关。本研究旨在探讨长期孤立性血小板减少症（PT）的发病机制。我们通过流式细胞术分析了在有或没有PT的allo-HSCT受者的骨髓（BM）和外周血（PB）中+90天时CD 4和CD 8 T细胞上CX 3CR 1的表达。然后我们在体外直接或在去除CD 8 +T细胞或将纯化的自体CD 8 + T细胞加入CD 8 +T-dep MNCs后，测定了有或无PT的受体的巨核细胞倍体分布、凋亡率和Fas表达。我们发现PT患者BM中CD 8 +T细胞的百分比高于对照组。CX 3CR 1的高表达与PT相关。PT组受者巨核细胞低倍体率明显增高。CD 8 +T细胞耗竭后巨核细胞凋亡增加，Fas表达降低，但可通过补充纯化的自体CD 8 +T细胞来纠正。多因素分析显示，+90 d时骨髓中CD 8 +T细胞和CD 8 +/CX 3CR 1 +T细胞的增加是PT的独立危险因素。我们的数据表明，骨髓中的CD 8 +T细胞的募集可能解释了巨核细胞凋亡的抑制，通过在PT中的CX 3CR 1+的表达升高allo-HSCT后。CX 3CR 1可能成为PT患者治疗的新靶点。
Prolonged isolated thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is associated with a poor prognosis. This study aimed to investigate the pathogenesis of prolonged isolated thrombocytopenia (PT). We analysed the expression of CX3CR1 on CD4 and CD8 T cells in bone marrow (BM) and peripheral blood (PB) at +90 days from allo-HSCT recipients with or without PT by flow cytometry analyses. We then determined the megakaryocytes ploidy distributions, apoptosis rate and Fas expression of recipients with or without PT in vitro directly or after depleting CD8+T cells or adding purified autologous CD8+T cells to CD8+T-dep MNCs. We found that the percentage of CD8+T cells in BM was higher in the patients with PT than in the controls. The elevated expression of the CX3CR1 was associated with PT. There was a marked increase in the percentage of low ploidy megakaryocytes in the recipients with PT. The depletion of CD8+T cells increased the apoptosis of megakaryocytes and decreased the expression of Fas, which could be corrected by re-adding purified autologous CD8+T cells. The increase of CD8+T cells and CD8+/CX3CR1+T cells in BM at +90 days were independent risk factors for PT according to multivariate analysis. Our data implied that the recruitment of CD8+T cells into BM might explain the suppression of megakaryocyte apoptosis through the elevated expression of CX3CR1+in PT after allo-HSCT. CX3CR1 might be a novel treatment target in recipients with PT.