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受体相互作用蛋白激酶-3参与甲型H1N1流感病毒感染小鼠记忆性CD8 T细胞的应答

  • 秦波音 ,
  • 王超 ,
  • 刘洋 ,
  • 任晓楠 ,
  • 方钟 ,
  • 李顺 ,
  • 周晓辉
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  • 复旦大学附属公共卫生临床中心,上海 201508

收稿日期: 2020-04-03

  网络出版日期: 2020-08-25

基金资助

“十三五”国家重点研发计划(2016YFD0500208),重点传染病防治国家科技重大专项(2017ZX10304402、2017ZX10304402),国家自然科学基金(81471397、31601908),上海市公共卫生临床中心院内项目(KY-GW-2018-48、KY-GW-2019-19)

Receptor-interacting protein kinase 3 plays a role in induction viral antigen specific CD8memory T cell responses against influenza A (H1N1) virus infection in mice

  • QIN Boyin ,
  • WANG Chao ,
  • LIU Yang ,
  • REN Xiaonan ,
  • FANG Zhong ,
  • LI Shun ,
  • ZHOU Xiaohui
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  • Shanghai Public Health Clinical Center , Fudan University, Shanghai 201508, China

Received date: 2020-04-03

  Online published: 2020-08-25

摘要

受体相互作用蛋白激酶-3(receptor-interacting protein kinase 3, RIPK3)是坏死复合体的关键成分之一,介导细胞程序性死亡(programmed cell death,PCD)的发生。前期研究发现流感抗原特异性CD8T细胞的初次应答部分依赖于RIPK3分子,为探讨其在记忆性CD8T细胞应答中的作用,对初次感染后的C57BL/6小鼠在免疫记忆阶段进行了再次感染,并用流式细胞仪检测了流感病毒特异性的记忆性CD8T细胞的表型和功能。结果发现小鼠初次感染甲型 H1N1流感病毒株A/Puerto Rico/8/34后37 d, RIPK3敲除小鼠的CD8T细胞比例及分泌细胞因子γ-干扰素(IFN-γ)和肿瘤坏死因子-α(TNF-α)的能力均显著低于野生型小鼠;在再次感染相同病毒时,RIPK3敲除小鼠流感病毒特异性CD8T细胞比例及分泌细胞因子IFN-γ的能力依旧显著低于野生型小鼠;而CD8中枢型记忆性T细胞(TCM)比例显著高于野生型小鼠,效应型记忆性T细胞(TEM)或效应性T细胞(TEff)比例却显著低于野生型小鼠。提示RIPK3分子参与调节流感病毒特异的记忆性CD8T细胞诱生数量和分泌细胞因子功能,并影响其TCM与TEM/TEff的比例,为深入探索病毒特异的记忆性CD8T细胞应答的分子机制提供了新线索。

本文引用格式

秦波音 , 王超 , 刘洋 , 任晓楠 , 方钟 , 李顺 , 周晓辉 . 受体相互作用蛋白激酶-3参与甲型H1N1流感病毒感染小鼠记忆性CD8 T细胞的应答[J]. 微生物与感染, 2020 , 15(4) : 213 -219 . DOI: 10.3969/j.issn.1673-6184.2020.04.003

Abstract

Receptor-interacting protein kinase 3 (RIPK3) is one of the key components of necrotic complex, which mediates the development of programmed cell necrosis. Our previous studies have revealed that the initial response of total influenza antigen-specific CD8T cells is partially dependent on RIPK3, but its role in memory CD8T cell response is unclear yet. In this study, we observed that the frequency of influenza specific CD8T cells and their ability to secrete cytokine IFN-γ and TNF-α in RIPK3 knockout mice were significantly lower than those in wild-type mice 37 days after the initial infection of H1N1 A/Puerto Rico/8/34 strain (PR8) in C57BL/6 mice. After the re-challenging infection of H1N1virus PR8, the frequency of viral specific CD8T cells and their ability to secrete cytokine IFN-γ in RIPK3 knockout mice were still significantly lower than those in wild-type mice. In addition, while the frequency of CD8central memory T cells (TCM) in RIPK3 knockout mice was significantly higher than that in wild-type mice, the proportion of effective memory T cells (TEM) or effective T cells (TEff) was significantly lower than that in wild-type mice. These results indicate that RIPK3 is involved in the regulation of the number and secretion of cytokines of influenza virus specific memory CD8T cells, and affects the ratio of TCM to TEM or TEff in memory CD8T cells, which provide new clues for further exploring the molecular mechanism of virus specific memory CD8T cell response.
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