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恒河猴髓系来源的抑制性细胞具有T细胞抑制功能,且在疫苗接种后短暂增加。

Rhesus Macaque Myeloid-Derived Suppressor Cells Demonstrate T Cell Inhibitory Functions and Are Transiently Increased after Vaccination.

作者信息

Lin Ang, Liang Frank, Thompson Elizabeth A, Vono Maria, Ols Sebastian, Lindgren Gustaf, Hassett Kimberly, Salter Hugh, Ciaramella Giuseppe, Loré Karin

机构信息

Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden.

Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

出版信息

J Immunol. 2018 Jan 1;200(1):286-294. doi: 10.4049/jimmunol.1701005. Epub 2017 Nov 27.

Abstract

Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence T cell responses in temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which is critical for late-stage vaccine testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs can be detected using several of the markers used in humans. However, whereas rhesus M-MDSCs lacked expression of CD33, PMN-MDSCs were identified as CD33 low-density neutrophils. Importantly, both M-MDSCs and PMN-MDSCs showed suppression of T cell proliferation in vitro. The frequency of circulating MDSCs rapidly and transiently increased 24 h after vaccine administration. M-MDSCs infiltrated the vaccine injection site, but not vaccine-draining lymph nodes. This was accompanied by upregulation of genes relevant to MDSCs such as arginase-1, IDO1, PDL1, and IL-10 at the injection site. MDSCs may therefore play a role in locally maintaining immune balance during vaccine-induced inflammation.

摘要

髓系来源的抑制性细胞(MDSCs)是多种病理状态下T细胞反应的主要调节因子。在诸如接种疫苗后出现的短暂炎症中,MDSCs是否会增加并影响T细胞反应尚不清楚。利用对晚期疫苗测试至关重要的恒河猴模型,我们证明可以使用人类中使用的几种标志物检测到单核细胞(M)-MDSCs和多形核(PMN)-MDSCs。然而,恒河猴M-MDSCs缺乏CD33表达,而PMN-MDSCs被鉴定为CD33低密度中性粒细胞。重要的是,M-MDSCs和PMN-MDSCs在体外均显示出对T细胞增殖的抑制作用。接种疫苗后24小时,循环MDSCs的频率迅速且短暂地增加。M-MDSCs浸润到疫苗注射部位,但未浸润到引流疫苗的淋巴结。这伴随着注射部位与MDSCs相关的基因如精氨酸酶-1、吲哚胺2,3-双加氧酶1(IDO1)、程序性死亡受体配体1(PDL1)和白细胞介素-10的上调。因此,MDSCs可能在疫苗诱导的炎症过程中在局部维持免疫平衡方面发挥作用。

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