Th17-Treg Antagonism: Impact on Disease Outcome in Helminth Infections

Th17-Treg 拮抗作用：对蠕虫感染疾病结果的影响

• 批准号: 42430697
• 负责人: Professor Dr. Achim Hoerauf
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/42430697?language=en
• 关键词: Th17; Treg; Antagonism; Impact; Disease

This project will investigate the molecular mechanisms involved in the induction of IgG4 subclass of immunoglobins by regulatory T-cells (Treg). Treg are important mediators of the well-known phenomena of immune suppression. There are distinct subgroups of antigenspecific and naturally occurring Treg that are induced in allergy during hypo-sensibilisation, in chronic infection like hepatitis C, or parasite infections. Our group described the occurrence at high frequency of antigen-specific Treg in human onchocerciasis, which was the first description of Treg in human infections at all. Subsequently, we have found that Treg clones selectively induce the synthesis of IgG4 when co-cultured with purified B cells. IgG4 are antiinflammatory and are up-regulated in allergy and chronic diseases, e.g. worm diseases. Based on our earlier results, the present project aims to find the molecular mechanisms of Treg-B cell interactions, and to determine which molecules (GITR, CTLA-4, ICOS, TLR etc., see Objectives) induce or inhibit these interactions. This work will be performed using cells from healthy donors stimulated with tetanus toxoid as antigen-model, and cells generated from onchocerciasis patients to extend the findings to a chronic helminth infection. These samples are available from earlier studies. The results from the project should have important implications for infectious diseases but also for allergy and auto-immune disorders.

本研究旨在探讨调节性T细胞（Treg）诱导IgG4亚类免疫球蛋白的分子机制。Treg是众所周知的免疫抑制现象的重要介质。存在抗原特异性和天然存在的Treg的不同亚组，其在低致敏期间的变态反应中、在慢性感染如丙型肝炎或寄生虫感染中诱导。我们的小组描述了人类盘尾丝虫病中抗原特异性Treg的高频率发生，这是人类感染中Treg的首次描述。随后，我们发现当与纯化的B细胞共培养时，Treg克隆选择性地诱导IgG 4的合成。IgG4在变态反应和慢性疾病（例如蠕虫病）中是稳定的并且上调。基于我们早期的结果，本项目旨在寻找Treg-B细胞相互作用的分子机制，并确定哪些分子（GITR、CTLA-4、ICOS、TLR等），（见目的）诱导或抑制这些相互作用。这项工作将使用破伤风类毒素刺激的健康供体细胞作为抗原模型，并从盘尾丝虫病患者中产生细胞，以将研究结果扩展到慢性蠕虫感染。这些样本来自早期的研究。该项目的结果应该对传染病以及过敏和自身免疫疾病具有重要意义。