权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Generation of memory T-cells in allergic diseases

过敏性疾病中记忆 T 细胞的产生

基本信息

批准号：
246259889
负责人：
Professorin Dr. Monika Christine Brunner-Weinzierl
金额：
--
依托单位：
Universitätskinderklinik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/246259889?language=en
关键词：
Generation memory cells allergic diseases

项目摘要

A prerequisite of the cure of allergic diseases is the elimination/suppression of its driving chronic immune responses directed against harmless substances of the environment such as allergens of the house dust mite or of birch pollen. T helper (TH2)-lymphocytes play a major role in the regulation of IgE-mediated allergc diseases. Allergen-specific TH2-lymphocytes persist long after the last challenge with allergens which implicates the presence of a TH-memory response. A successful immunotherapy correlates well with a reduction of the allergen-specific response of TH2-lymphocytes. Our previous data suggest that the quality of TH-memory responses in vivo is regulated by CTLA-4, a inhibitory molecule expressed at the cell surface of T lymphocytes. The effect is mediated via cell-intrinsic signalling of TH lymphocytes as well as cell-extrinsic mechanisms by other cells. The latter might be mediated by regulatory T-cells (Treg) which express CTLA-4 constitutively and use it to accomplish suppressive function. Aim of the project is to understand the molecular and cellular basis of the quantitative as well as qualitative regulation of the memory response of allergic diseases. In this respect, we will determine the role of CTLA-4-signals of different cell populations during the generation of memory subpopulations, with special emphasis on the role of Treg-cells. In addition, the CTLA-4-mediated manipulation of the quality and quantity of memory responses will be correlated with severity codes of allergis diseases. Here, we will also determine the impact of successful allergen-desensitising treatment on the cellular composition of the memory compartment. Altogether, the study will give general insights on the TH memory compartment of allergic diseases and will show whether the disruption of CTLA-4-mediated memory formation could be an option for therapeutic interventions of allergic diseases.

治疗过敏性疾病的先决条件是消除/抑制其针对环境中无害物质的驱动慢性免疫应答，例如屋尘螨或桦树花粉的过敏原。辅助性T淋巴细胞（Th 2）在IgE介导的变态反应性疾病的调节中起主要作用。过敏原特异性TH 2-淋巴细胞在最后一次过敏原激发后持续很长时间，这意味着TH记忆应答的存在。成功的免疫疗法与TH 2-淋巴细胞的变应原特异性应答的降低密切相关。我们以前的数据表明，在体内的TH-记忆反应的质量是由CTLA-4，在T淋巴细胞的细胞表面表达的抑制分子调节。该效应通过TH淋巴细胞的细胞内在信号传导以及其他细胞的细胞外在机制介导。后者可能是由组成型表达CTLA-4的调节性T细胞（Treg）介导的，并利用它来实现抑制功能。该项目的目的是了解过敏性疾病记忆反应的定量和定性调节的分子和细胞基础。在这方面，我们将确定CTLA-4-信号的不同细胞群体在记忆亚群的产生过程中的作用，特别强调Treg细胞的作用。此外，CTLA-4介导的对记忆反应的质量和数量的操纵将与过敏性疾病的严重程度代码相关。在这里，我们还将确定成功的过敏原脱敏治疗对记忆舱的细胞组成的影响。总之，该研究将提供关于过敏性疾病的TH记忆区室的一般见解，并将显示CTLA-4介导的记忆形成的破坏是否可以作为过敏性疾病的治疗干预的一种选择。