Li Shuguang, Wang Lin, Zhao Chunhong, Li Lizhen, Peng Jun, Hou Ming
Haematology Oncology Centre, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Br J Haematol. 2007 Nov;139(4):605-11. doi: 10.1111/j.1365-2141.2007.06737.x.
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.
为了研究骨髓中CD8 + T细胞对特发性血小板减少性紫癜(ITP)患者自体巨核细胞生成的影响及其机制,我们从15例慢性ITP患者和13例对照者中制备了骨髓单个核细胞(MNC)。将MNC在半固体和液体培养系统中直接进行体外培养(MNC组),或在去除CD8 + T细胞后培养(CD8 + T细胞去除组),或将纯化的自体CD8 + T细胞添加到去除CD8 + T细胞的MNC中进行共培养(共培养组),或在共培养中添加地塞米松(DEX组)。检测巨核细胞的数量和质量。慢性ITP患者自体CD8 + T细胞存在时巨核细胞计数增加,而血小板生成减少。此外,观察到多倍体和凋亡巨核细胞的百分比降低,上清液中可溶性Fas(sFas)水平升高。地塞米松成功纠正了CD8 + T细胞对自体巨核细胞生成的这种影响。这些研究提供了证据,表明慢性ITP患者骨髓中活化的CD8 + T细胞可能抑制巨核细胞凋亡,导致血小板生成受损。巨核细胞凋亡可能是ITP治疗的一个新靶点。