Analysis of the effect of S mansomi infection on regulatory T cell development and function

S mansomi感染对调节性T细胞发育和功能的影响分析

• 批准号: BB/D522903/1
• 负责人: Anne Cooke
• 金额: $ 38.64万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD522903%2F1
• 关键词: Analysis; effect; mansomi; infection; regulatory

The immune response to antigen is regulated in a variety of ways including by regulatory T cells (T regs). An over exuberant immune response to antigen can be detrimental and could cause tissue damage. Following infection with a helminth such as S. mansoni there is good evidence to show that immune responses are dampened down. For example, it has been shown that allergic responses are diminished and also that autoimmunity, where the immune system destroys self tissue, is inhibited. We and others have shown that following exposure to S. mansoni antigens T regs are induced. NOD mice have been shown to have defects in T reg function and this might represent one of the predisposing features for development in autoimmunity. We find that following exposure to S. mansoni antigens there is an increase in T cell production of IL-10, a marker of T reg activity. Naturally arising and induced T regs have different functional characteristics and it is unclear whether the T regs induced by S. mansoni fall into both categories or only one of them. Regulatory T cells are known not oly to be induced by IL-10 but also TGFbeta both of which are elicited in the mammalian host by exposure to schistosomal antigens. We propose to characterise the T regs induced during infection with S. mansoni and exposure to schistosome antigens in normal mice and in NOD mice with their known defects in T reg activity. In this way we will be able to define not only the mechanisms by which this induction of T regs occurs but also have the potential to identify schistosome derived molecules mediating this effect. This could lead to the identification of novel biomodulators that might have potential in the treatment of inflammatory conditions such as autoimmunity and inflammatory bowel disease.

对抗原的免疫应答以多种方式调节，包括通过调节性T细胞（T细胞）。对抗原的过度免疫应答可能是有害的，并可能导致组织损伤。在感染蠕虫如S. mansoni有很好的证据表明免疫反应被抑制了。例如，已经表明，过敏反应被减弱，并且自身免疫（其中免疫系统破坏自身组织）也被抑制。我们和其他人已经表明，在接触S。诱导曼氏抗原T细胞。NOD小鼠已被证明具有T reg功能缺陷，这可能代表了自身免疫发展的诱发特征之一。我们发现，在暴露于S。mansoni抗原，则T细胞产生IL-10（T reg活性的标志物）增加。天然产生的和诱导的T细胞具有不同的功能特性，目前尚不清楚S. mansoni属于这两类或其中之一。已知调节性T细胞不仅由IL-10诱导，而且也由TGF β诱导，两者都是通过暴露于溶酶体抗原在哺乳动物宿主中引发的。我们建议消除S. mansoni和暴露于正常小鼠和NOD小鼠中的溶酶体抗原，NOD小鼠具有已知的T reg活性缺陷。通过这种方式，我们不仅能够确定这种诱导T细胞发生的机制，而且还可能鉴定介导这种效应的溶酶体衍生分子。这可能会导致识别新的生物调节剂，可能有潜力在治疗炎症性疾病，如自身免疫和炎症性肠病。

项目成果

Parasitic worms and inflammatory diseases.

寄生虫和炎症性疾病。

• DOI: 10.1111/j.1365-3024.2006.00879.x
• 发表时间: 2006-10
• 期刊: PARASITE IMMUNOLOGY
• 影响因子: 2.2
• 作者: Zaccone, P;Fehervari, Z;Phillips, J M;Dunne, D W;Cooke, A
• 通讯作者: Cooke, A