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衰老会损害传统树突状细胞在用TLR7配体刺激时交叉启动CD8 + T细胞的能力。

Aging Impairs the Ability of Conventional Dendritic Cells to Cross-Prime CD8+ T Cells upon Stimulation with a TLR7 Ligand.

作者信息

Zacca Estefanía R, Crespo María I, Acland Rachel P, Roselli Emiliano, Núñez Nicolás G, Maccioni Mariana, Maletto Belkys A, Pistoresi-Palencia María C, Morón Gabriel

机构信息

Centro de Investigaciones en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

出版信息

PLoS One. 2015 Oct 16;10(10):e0140672. doi: 10.1371/journal.pone.0140672. eCollection 2015.

Abstract

The aging process is accompanied by altered immune system functioning and an increased risk of infection. Dendritic cells (DCs) are antigen-presenting cells that play a key role in both adaptive and innate immunity, but how aging affects DCs and their influence on immunity has not been thoroughly established. Here we examined the function of conventional DCs (cDCs) in old mice after TLR7 stimulation, focusing on their ability to cross-prime CD8+ T cells. Using polyU, a synthetic ssRNA analog, as TLR7 ligand and OVA as an antigen (Ag) model, we found that cDCs from old mice have a poor ability to stimulate a CD8+ T cell-mediated cytotoxic response. cDCs from old mice exhibit alterations in Ag-processing machinery and TLR7 activation. Remarkably, CD8α+ cDCs from old mice have an impaired ability to activate naïve CD8+ T cells and, moreover, a lower capacity to mature and to process exogenous Ag. Taken together, our results suggest that immunosenescence impacts cDC function, affecting the activation of naïve CD8+ T cells and the generation of effector cytotoxic T cells.

摘要

衰老过程伴随着免疫系统功能的改变以及感染风险的增加。树突状细胞(DCs)是抗原呈递细胞,在适应性免疫和先天性免疫中均发挥关键作用,但衰老如何影响DCs及其对免疫的影响尚未完全明确。在此,我们研究了老年小鼠经TLR7刺激后常规DCs(cDCs)的功能,重点关注其交叉启动CD8+ T细胞的能力。使用聚尿苷酸(一种合成的单链RNA类似物)作为TLR7配体,卵清蛋白(OVA)作为抗原(Ag)模型,我们发现老年小鼠的cDCs刺激CD8+ T细胞介导的细胞毒性反应的能力较差。老年小鼠的cDCs在抗原加工机制和TLR7激活方面表现出改变。值得注意的是,老年小鼠的CD8α+ cDCs激活初始CD8+ T细胞的能力受损,此外,其成熟和加工外源性抗原的能力也较低。综上所述,我们的结果表明免疫衰老影响cDC功能,影响初始CD8+ T细胞的激活以及效应细胞毒性T细胞的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f740/4608578/2401fcde2b6c/pone.0140672.g001.jpg

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