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被感染的树突状细胞对细胞毒性 CD8 T 细胞的抗原特异性激活。

Antigen specific activation of cytotoxic CD8 T cells by infected dendritic cells.

机构信息

Universite Claude Bernard Lyon 1, Centre International de Recherche en Infectiologie, Inserm U1111, CNRS UMR5308, École Normale Supérieure de Lyon, Lyon, France.

出版信息

Front Cell Infect Microbiol. 2023 Oct 26;13:1245299. doi: 10.3389/fcimb.2023.1245299. eCollection 2023.

DOI:10.3389/fcimb.2023.1245299
PMID:37953797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10639145/
Abstract

() is a pathogen associated with a wide variety of diseases, from minor to life-threatening infections. Antibiotic-resistant strains have emerged, leading to increasing concern about the control of infections. The development of vaccines may be one way to overcome these resistant strains. However, ability to internalize into cells - and thus to form a reservoir escaping humoral immunity - is a challenge for vaccine development. A role of T cells in the elimination of persistent has been established in mice but it remains to be established if CD8 T cells could display a cytotoxic activity against infected cells. We examined the ability of CD8 T cells to recognize and kill dendritic cells infected with We first evidenced that both primary mouse dendritic cells and DC2.4 cell line can be infected with . We then generated a strain of expressing a model CD8 epitope and transgenic F5 CD8 T cells recognizing this model epitope were used as reporter T cells. In response to -infected dendritic cells, F5 CD8 T cells produced IFN-γ in an antigen-specific manner and displayed an increased ability to kill infected cells. Altogether, these results demonstrate that cells infected by display bacteria-derived epitopes at their surface that are recognized by CD8 T cells. This paves the way for the development of CD8 T cell-based therapies against .

摘要

() 是一种与多种疾病相关的病原体,从轻微感染到危及生命的感染都有可能。已经出现了对抗生素耐药的菌株,这导致人们越来越关注感染的控制。疫苗的开发可能是克服这些耐药菌株的一种方法。然而,能够内化到细胞中——从而形成逃避体液免疫的储库——是疫苗开发的一个挑战。在小鼠中已经确立了 T 细胞在消除持续性感染中的作用,但 CD8 T 细胞是否能够对感染细胞显示细胞毒性作用仍有待确定。我们研究了 CD8 T 细胞识别和杀死感染的树突状细胞的能力。我们首先证明了原代小鼠树突状细胞和 DC2.4 细胞系都可以被感染。然后,我们生成了一株表达模型 CD8 表位的,并使用识别该模型表位的转基因 F5 CD8 T 细胞作为报告 T 细胞。在对感染的树突状细胞的反应中,F5 CD8 T 细胞以抗原特异性的方式产生 IFN-γ,并显示出增强的杀伤感染细胞的能力。总之,这些结果表明,被感染的细胞表面展示了源自细菌的表位,这些表位被 CD8 T 细胞识别。这为开发针对感染的 CD8 T 细胞为基础的治疗方法铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/736dd9c9df09/fcimb-13-1245299-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/e4fec1307173/fcimb-13-1245299-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/d989c70b2bcc/fcimb-13-1245299-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/7e7454594312/fcimb-13-1245299-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/736dd9c9df09/fcimb-13-1245299-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/e4fec1307173/fcimb-13-1245299-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/d989c70b2bcc/fcimb-13-1245299-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/7e7454594312/fcimb-13-1245299-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4507/10639145/736dd9c9df09/fcimb-13-1245299-g004.jpg

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