Generation of memory T-cells in allergic diseases

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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.