CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura
CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura
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DOI：
10.1111/j.1365-2141.2007.06737.x
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发表时间：
2007-11-01
影响因子：
6.5
通讯作者：
Hou, Ming
中科院分区：
文献类型：
--
作者：
Li, Shuguang;Wang, Lin;Hou, Ming
为探讨CD 8（+）T细胞在特发性血小板减少性紫癜（ITP）患者自体巨核细胞生成中的作用及其机制，我们制备了15例慢性ITP患者和13例对照者的骨髓单个核细胞（MNCs）。方法：采用半固体和液体培养系统，分别在体外直接培养（MNC组）、去除CD 8（+）T细胞（CD 8（+）T-dep组）、加入纯化的自体CD 8（+）T细胞（共培养组）和加入地塞米松（DEX组）。检测巨核细胞的数量和质量。慢性ITP患者自体CD 8（+）T细胞存在时，巨核细胞计数增加，而血小板生成减少。此外，在上清液中观察到较低的倍数体和凋亡巨核细胞的百分比以及较高水平的可溶性Fas（sFas）。地塞米松成功地纠正了CD 8（+）T细胞对自体巨核细胞生成的影响。这些研究提供了证据表明，慢性ITP患者骨髓中活化的CD 8（+）T细胞可能抑制巨核细胞凋亡，导致血小板生成受损。巨核细胞凋亡可能成为治疗ITP的新靶点。
To investigate the effect and mechanism of the CD8(+) T cells in bone marrow on autologous megakaryocytopoiesis in idiopathic thrombocytopenic purpura (ITP) patients, we prepared bone marrow mononuclear cells (MNCs) from 15 chronic ITP patients and 13 controls. MNCs were cultured in vitro directly (MNC group) or after depleting CD8(+) T cells (CD8(+) T-dep group) or adding purified autologous CD8(+) T cells to CD8(+) T-dep MNCs (Coculture group) or adding dexamethasone to the coculture (DEX group) all in semi-solid and liquid culture systems. The quantity and quality of megakaryocytes were measured. The megakaryocyte count was increased in the presence of autologous CD8(+) T cells of patients with chronic ITP, while platelet production was reduced. In addition, lower percentages of polyploidy and apoptotic megakaryocytes, and higher levels of soluble Fas (sFas) in supernatant were observed. Dexamethasone successfully corrected this effect of CD8(+) T cells on autologous megakaryocytopoiesis. These studies provide evidence that activated CD8(+) T cells in bone marrow of patients with chronic ITP might suppress megakaryocyte apoptosis, leading to impaired platelet production. Megakaryocyte apoptosis would be a novel target for the management of ITP.