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先前经美洲钩虫幼虫抗原刺激的鼠骨髓树突状细胞可扩增调节性 T 淋巴细胞。

Expansion of T regulatory lymphocytes by murine bone marrow dendritic cells previously stimulated with Anisakis simplex larval antigens.

机构信息

Universidad Complutense, Facultad de Farmacia, Departamento de Microbiología y Parasitología, Madrid, Spain.

Hospital Arnau de Vilanova, Departamento de Investigación, Valencia, Spain.

出版信息

Mem Inst Oswaldo Cruz. 2021 Feb 5;116:e200560. doi: 10.1590/0074-02760200560. eCollection 2021.

Abstract

BACKGROUND

Anisakis simplex antigens present immunomodulatory properties by the induction of tolerogenic dendritic cells (DCs) in mice.

OBJECTIVES

To study the capacity of DCs stimulated with A. simplex excretory-secretory (ES) or crude extract (CE) to generate Tregs. To investigate in vitro effects of antigens on the metabolic activity of splenocytes induced by LPS or CpG.

METHODS

Phenotypic and functional characterization of T cells co-cultured with A. simplex-pulsed DCs was performed by flow cytometry. Lymphocyte mitochondrial respiratory activity was estimated by the Alamar Blue® Assay.

FINDINGS

In C57BL/6J, CD4+CD25-Foxp3+ and CD8+CD25-Foxp3+ populations increased by CE-stimulated-DCs. In BALB/c, CE-stimulated-DCs caused the expansion of CD4+CD25+Foxp3+IL-10+ and CD8+CD25+Foxp3+IL-10+. IFN-γ expression raised in BALB/c CD4+CD25+ and CD4+CD25- for CE and ES, respectively. ES-stimulated-DCs increased CD4+CD25+ Foxp3+ and CD8+CD25- Foxp3+ expression in T cells. The association of ES or CE with LPS produced the increase in splenocyte activity in C57BL/6J. The association of CE with CpG decreased the proliferation caused by CpG in C57BL/6J.

MAIN CONCLUSIONS

A. simplex increase the frequency of Tregs, which in turn produce IL-10 and IFN-γ. The host genetic base is essential in the development of anti-Anisakis immune responses (Th2, Th1, Treg).

摘要

背景

曼氏迭宫绦虫(Anisakis simplex)的排泄分泌产物(ES)或粗提物(CE)可诱导产生具有免疫调节功能的耐受型树突状细胞(DC)。

目的

研究用 A. simplex ES 或 CE 刺激的 DC 产生 Treg 的能力。研究抗原在 LPS 或 CpG 诱导的脾细胞代谢活性方面的体外效应。

方法

通过流式细胞术对与 A. simplex 脉冲 DC 共培养的 T 细胞进行表型和功能特征分析。通过 Alamar Blue®测定法评估淋巴细胞线粒体呼吸活性。

结果

在 C57BL/6J 中,CE 刺激的 DC 增加了 CD4+CD25-Foxp3+和 CD8+CD25-Foxp3+群体。在 BALB/c 中,CE 刺激的 DC 导致 CD4+CD25+Foxp3+IL-10+和 CD8+CD25+Foxp3+IL-10+的扩增。CE 分别引起 BALB/c CD4+CD25+和 CD4+CD25-的 IFN-γ表达增加。ES 刺激的 DC 增加了 T 细胞中 CD4+CD25+Foxp3+和 CD8+CD25-Foxp3+的表达。ES 或 CE 与 LPS 结合在 C57BL/6J 中增加了脾细胞的活性。CE 与 CpG 结合降低了 CpG 在 C57BL/6J 中引起的增殖。

主要结论

A. simplex 增加了 Treg 的频率,而 Treg 反过来又产生了 IL-10 和 IFN-γ。宿主遗传基础在抗曼氏迭宫绦虫免疫反应(Th2、Th1、Treg)的发展中至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d128/7874847/3ac6b18d248b/1678-8060-mioc-116-e200560-gf2.jpg

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