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淋巴细胞性脉络丛脑膜炎病毒克隆 13 感染导致二酰基甘油激酶 α 缺陷型小鼠的 CD8 T 细胞介导的宿主死亡。

Lymphocytic Choriomeningitis Virus Clone 13 Infection Results in CD8 T Cell-Mediated Host Mortality in Diacylglycerol Kinase α-Deficient Mice.

机构信息

Division of Pediatric Hematology, Oncology, and BMT, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.

Versiti Blood Research Institute, Milwaukee, WI.

出版信息

J Immunol. 2023 May 1;210(9):1281-1291. doi: 10.4049/jimmunol.2101011.

Abstract

Diacylglycerol is a potent element of intracellular secondary signaling cascades whose production is enhanced by cell-surface receptor agonism and function is regulated by enzymatic degradation by diacylglycerol kinases (DGKs). In T cells, stringent regulation of the activity of this second messenger maintains an appropriate balance between effector function and anergy. In this article, we demonstrate that DGKα is an indispensable regulator of TCR-mediated activation of CD8 T cells in lymphocytic choriomeningitis virus Clone 13 viral infection. In the absence of DGKα, Clone 13 infection in a murine model results in a pathologic, proinflammatory state and a multicellular immunopathologic host death that is predominantly driven by CD8 effector T cells.

摘要

二酰基甘油是细胞内二级信号级联反应的有力组成部分,其产生受细胞表面受体激动剂增强,功能受二酰基甘油激酶(DGK)的酶促降解调节。在 T 细胞中,这种第二信使活性的严格调节保持了效应功能和失能之间的适当平衡。在本文中,我们证明了 DGKα 是淋巴细胞性脉络丛脑膜炎病毒克隆 13 病毒感染中 TCR 介导的 CD8 T 细胞激活所必需的调节剂。在缺乏 DGKα 的情况下,在小鼠模型中感染克隆 13 会导致病理性、促炎状态和多细胞免疫病理宿主死亡,主要由 CD8 效应 T 细胞驱动。

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