CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.
CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.
复制标题
CD8 T 细胞在免疫性血小板减少症中通过血小板脱唾液酸作用诱导肝脏中的血小板清除
DOI：
10.1038/srep27445
复制
发表时间：
2016-06-20
影响因子：
4.6
通讯作者：
Hou M
中科院分区：
文献类型：
--
作者：
Qiu J;Liu X;Li X;Zhang X;Han P;Zhou H;Shao L;Hou Y;Min Y;Kong Z;Wang Y;Wei Y;Liu X;Ni H;Peng J;Hou M
除了抗血小板自身抗体外，CD 8+细胞毒性T淋巴细胞（CTL）在免疫性血小板减少症（ITP）中血小板破坏增加中起重要作用。最近的研究已经强调血小板去唾液酸化通过肝细胞去唾液酸糖蛋白受体（ASGPR）导致血小板清除。在ITP中CD 8 + T细胞是否诱导血小板去唾液酸化仍不清楚。在这里，我们研究了ITP患者CD 8 + T细胞对血小板的细胞毒性和血小板去唾液酸化。我们发现，新鲜血小板的去唾液酸化在CD 8 + T细胞的细胞毒性阳性的ITP患者显著高于无细胞毒性和对照组。在体外，CD 8 + T细胞从ITP患者与阳性细胞毒性诱导显着的血小板去唾液酸化，神经氨酸酶-1的表达在血小板表面，和血小板吞噬肝细胞。为了研究体内血小板存活和清除，免疫CD 61敲除小鼠并使用其CD 8+脾细胞。与这些CD 8+脾细胞共培养的血小板表现出循环中存活率降低和肝脏中吞噬作用增加。神经氨酸酶抑制剂和ASGPRs竞争剂均显著改善血小板存活率，并消除由CD 8+脾细胞引起的血小板清除。这些发现表明，CD 8 + T细胞诱导ITP肝脏中血小板去唾液酸化和血小板清除，这可能是ITP的一种新机制。
In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP.