Coincidence of autoantibody production with the activation of natural killer T cells in α-galactosylceramide-mediated hepatic injury
Coincidence of autoantibody production with the activation of natural killer T cells in α-galactosylceramide-mediated hepatic injury
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DOI：
10.1111/j.1365-2567.2011.03405.x
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发表时间：
2011-05-01
期刊：
影响因子：
6.4
通讯作者：
Abo, Toru
中科院分区：
文献类型：
--
作者：
Matsumoto, Hiroaki;Kawamura, Toshihiko;Abo, Toru
已知自然杀伤T（NKT）细胞通过与CD 1d的相互作用被α-半乳糖神经酰胺（α-GalCer）特异性激活。此时，NKT细胞介导自身反应性并最终诱导肝损伤。由于这些免疫应答类似于急性自身免疫性肝炎，因此研究了自身抗体产生和自身抗体产生B-1细胞的活化是否伴随着这种现象。当用α-GalCer处理小鼠时，早在第3天就在血清中检测到针对Hep-2细胞和双链DNA的自身抗体（在第14天显示峰值）。第3天，肝脏中出现B220 low细胞。这些B220低细胞为CD 5-（即B-1 B细胞）和CD 69+（活化标志物）。首先，这种B220低细胞存在于腹膜腔中，但即使在该部位，B220低细胞的比例也随着α-GalCer的施用而增加。与肝脏中B220 low细胞的出现平行，在脂多糖存在下，肝淋巴细胞在体外细胞培养中获得了产生自身抗体的潜力。这些结果表明，由α-GalCer给药诱导的肝损伤类似于急性自身免疫性肝炎，并且主要效应淋巴细胞是具有自身反应性的NKT细胞和产生自身抗体的B-1细胞。
P>Natural killer T (NKT) cells are known to be specifically activated by alpha-galactosylceramide (alpha-GalCer) via their interaction with CD1d. At that time, NKT cells mediate autoreactivity and eventually induce hepatic injury. As these immune responses resemble acute autoimmune hepatitis, it was examined whether autoantibody production and the activation of autoantibody-producing B-1 cells were accompanied by this phenomenon. Autoantibodies against Hep-2 cells and double-stranded DNA were detected in sera as early as day 3 (showing a peak at day 14) when mice were treated with alpha-GalCer. On day 3, B220low cells appeared in the liver. These B220low cells were CD5- (i.e. B-1b cells) and CD69+ (an activation marker). Primarily, such B220low cells were present in the peritoneal cavity, but the proportion of B220low cells increased with the administration of alpha-GalCer even at this site. In parallel with the appearance of B220low cells in the liver, hepatic lymphocytes acquired the potential to produce autoantibodies in in vitro cell culture in the presence of lipopolysaccharide. These results suggested that hepatic injury induced by alpha-GalCer administration resembled acute autoimmune hepatitis and that the major effector lymphocytes were NKT cells with autoreactivity and autoantibody-producing B-1 cells.