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凋亡缺陷增加了 Bim-/-Faslpr/lpr 小鼠感染后的记忆性 CD8+ T 细胞。

Defects in apoptosis increase memory CD8+ T cells following infection of Bim-/-Faslpr/lpr mice.

机构信息

Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

出版信息

Cell Immunol. 2011;271(2):256-66. doi: 10.1016/j.cellimm.2011.07.003. Epub 2011 Jul 24.

DOI:10.1016/j.cellimm.2011.07.003
PMID:21839428
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3196032/
Abstract

During many infections, large numbers of effector CD8(+) T cells are generated. After pathogen clearance, the majority of these cells undergo apoptosis, while the survivors differentiate into memory CD8(+) T cells. Although loss of both Bim and Fas function dramatically increased antigen-specific CD8(+) T cells in the lymph nodes following acute lymphocytic choriomeningitis virus (LCMV) infection, it was unclear whether they were pardoned effector or true memory CD8(+) T cells. In this study, we demonstrate they are bona fide memory T cells as characterized by surface marker expression, cytokine production, homeostatic proliferation, and ability to clear a secondary challenge of pathogen. Loss of both Bim and Fas also increased the number of virus-specific CD4(+) T cells found in the lymph nodes compared to the parental genotypes or wildtype mice. These studies illustrate that decreasing apoptosis increases the number of memory T cells and therefore could increase the efficacy of vaccines.

摘要

在许多感染中,会产生大量的效应性 CD8(+) T 细胞。病原体清除后,这些细胞中的大多数会发生凋亡,而存活下来的细胞则分化为记忆性 CD8(+) T 细胞。尽管 Bim 和 Fas 功能缺失都显著增加了急性淋巴细胞脉络丛脑膜炎病毒 (LCMV) 感染后淋巴结中抗原特异性 CD8(+) T 细胞的数量,但尚不清楚它们是被赦免的效应细胞还是真正的记忆性 CD8(+) T 细胞。在这项研究中,我们通过表面标志物表达、细胞因子产生、稳态增殖和清除病原体二次挑战的能力证明它们是真正的记忆 T 细胞。与亲本基因型或野生型小鼠相比,Bim 和 Fas 双缺失也增加了淋巴结中病毒特异性 CD4(+) T 细胞的数量。这些研究表明,减少细胞凋亡会增加记忆 T 细胞的数量,从而提高疫苗的疗效。

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本文引用的文献

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Apoptosis regulators Bim and Fas function concurrently to control autoimmunity and CD8+ T cell contraction.凋亡调节因子Bim和Fas协同发挥作用,以控制自身免疫和CD8 + T细胞收缩。
Immunity. 2008 Feb;28(2):218-30. doi: 10.1016/j.immuni.2007.12.014.
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Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity.凋亡调节因子Fas和Bim协同作用,关闭慢性免疫反应并预防自身免疫。
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7
Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor.炎症通过T-bet转录因子的分级表达来指导记忆前体细胞和短期效应性CD8(+) T细胞的命运。
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Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity.树突状细胞中Bim的缺乏会导致淋巴细胞过度激活和自身免疫。
Blood. 2007 May 15;109(10):4360-7. doi: 10.1182/blood-2006-11-056424. Epub 2007 Jan 16.
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Role of Bim in regulating CD8+ T-cell responses during chronic viral infection.Bim在慢性病毒感染过程中调节CD8 + T细胞反应中的作用。
J Virol. 2006 Sep;80(17):8627-38. doi: 10.1128/JVI.00855-06.
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Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory.Bim介导CD127(低表达)效应T细胞的凋亡并限制T细胞记忆。
Eur J Immunol. 2006 Jul;36(7):1694-706. doi: 10.1002/eji.200635897.