Generation of memory T-cells in allergic diseases

治疗过敏性疾病的一个先决条件是消除/抑制其针对无害环境物质的慢性免疫反应，如屋尘螨或桦树花粉的过敏原。辅助性T细胞(TH2)在调节IgE介导的过敏性疾病中发挥重要作用。过敏原特异的TH2淋巴细胞在最后一次与过敏原的挑战后持续很长时间，这意味着存在TH记忆反应。一种成功的免疫治疗与减少TH2淋巴细胞的过敏原特异性反应密切相关。我们以前的数据表明，体内TH记忆反应的质量受CTLA-4调节，CTLA-4是一种表达在T淋巴细胞细胞表面的抑制分子。这种作用是通过TH淋巴细胞的细胞内信号转导以及其他细胞的细胞外在机制来实现的。后者可能是由调节性T细胞(Treg)介导的，调节性T细胞结构性地表达CTLA-4并利用其完成抑制功能。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，我们将确定不同细胞群的CTLA-4信号在记忆亚群产生过程中的作用，特别是Treg细胞的作用。此外，CTLA-4介导的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隔室细胞组成的影响。总而言之，这项研究将对变态反应性疾病的记忆隔间提供一般性的见解，并将表明破坏CTLA-4介导的记忆形成是否可以作为过敏性疾病治疗干预的一种选择。

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.