Objective
Immune cell activity is regulated by both activating and inhibitory receptors, which transduce signals through two motifs: ITAM and ITIM, respectively. ITIM receptors play a key role in the regulation of ITAM induced activation of leukocytes, thus creating a balance, which regulates cellular functions and the outcome of the immune response (immune priming or tolerance).
Moreover aberrant expression of activating and/or inhibitory immune receptors and of their ligands can lead to deleterious effects, including autoimmunity. While inhibitory NK receptors are also often expressed by normal T cells, the activating counterparts are mostly found on pathogenic self reactive T cells in autoimmune diseases.
Transgenic mice expressing activating receptor Ly49D/DAP12 an d/or its inhibitory counterpart Ly49A (in presence/absence of H 2Dd as ligand) offer the opportunity to better understand the role of ITAM/ITIM balance in T cell biology, and the relevance of T cell ITAM signalling (via DAP12) in autoimmunity.
We first pro pose to address T lymphocyte differentiation in Ly49D/DAP12 transgenic mice, by studying thymocyte development and TCR repertoire selection. Peripheral T lymphocyte function will be investigated upon Ly49D engagement alone or in combination with TCR stimulation.
With the aim to assess the function of activating receptors expressed by CD8+ T cells in autoimmunity, a model of diabetes will be used (RIP-LCMV mice). The CD8+ T cells of the Ly49D/DAP12 transgenic mice will be will be transferred into RIP LCMV G P transgenic mice, whose beta islet cells express LCMV GP (lymphocytic choriomeningitis glycoprotein) as self antigen.
In this model, self-reactive CD8+ T cells trigger diabetes only upon adequate stimulation (e.g. LMCV infection, CD28/B7.2 costimulation). We will test whether ITAM signalling via Ly49D/DAP12 is sufficient to trigger diabetes. Consequently this approach might allow bringing new insight in autoimmunity to design novel appropriate treatments.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences cell biology
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
You need to log in or register to use this function
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-5
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
EPALINGES
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.