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Cell-mediated immune responses in health and diseases: from basic science to clinical investigation

Research project P6/12 (Research action P6)


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Description :

This consortium was designed to assemble a critical mass of knowledge and expertise enhancing Belgian competitiveness in the field of immunology and immunotherapy. For this purpose, the proposal has been organized in 6 workpackages with the aim of taking advantage of the complementary skills of the 6 partners in major areas of modern immunology. Our objective is to allow each team to deepen their expertise in a given field of immunology, to foster new collaborations within a series of workpackages, and to finally build a large, Belgian community-based, collaborative research and teaching consortium on Immunology.

Our project is centred on T cell development and function. Using a panel of human and murine models, we wish to explore the signals and factors driving T cell differentiation from their precursor stage to their final effector and or regulatory state. Basic knowledge or technological advances gained in a given project will be made immediately accessible to all partners of the network. It is expected that this continuous exchange of information - which will be facilitated by a dedicated website and regular meetings - will result in the emergence of original concepts and innovative approaches in the course of the research programme. Training activities will be organized around the major themes of the network. Special attention will be paid to exchanges of scientists between the partners, even for short periods of time, allowing the trainees to learn new conceptual and methodological approaches while keeping the focus of their research. A major aim of the network is to promote translational medical research based on fundamental scientific advances. The composition of the network which brings together basic scientists and physicians engaged in clinical research will obviously facilitate the implementation of translational research activities for which common platforms of cell therapy and immune monitoring are in place.

In order to facilitate the management of the network and to foster collaborations between the partners, the research programme was organized in 6 workpackages (WP).

Workpackage 1 aims at generating human T cells with antigen-specific activities from hematopoietic stem cells using an ex-vivo approach. The goal of these experiments is to generate cytotoxic T cells with potent anti-tumor activities.

Workpackage 2 is devoted to regulatory T cells which limit the efficacy of effector immune responses. Natural regulatory T cells at tumor sites will be analyzed in depth after isolation and T cell cloning and particular attention will be paid to their action on the process of presentation of tumor antigens. In parallel, efforts will be made to characterize new types of adaptative regulatory T cells controlling autoimmune and allergic disorders.

Workpackage 3 aims at designing new modes of activation of dendritic cells to enhance their capacity to induce protective T cell responses. For this purpose, we will take advantage of recent advances in Toll-like receptor signalling to design novel genetic and pharmacological tools.

Workpackage 4 will focus on factors and situations leading to biased helper T cell responses. Special efforts will be made to decipher the basis for biased helper T cell responses in early life using in vitro experiments and in vivo investigations. The newly ThB cell subset will be specifically addressed as well.

Workpackage 5 is devoted to studies on the complex action of indoleamine 2,3 dioxygenase, an enzyme that plays a critical role in the regulation of T cell-mediated immune responses.

Workpackage 6 will explore the environmental factors which influence the fate and function of effector T lymphocytes in target tissues. Special attention will be paid to the environment created by tumor cells and to the lung environment with the aim to gain insight into the pathogenesis of allergic pulmonary diseases.


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