Objective
The fine and complex regulation of CD4 immune response is important in cancer, autoimmune diseases, inflammatory disorders and viral infection. If signals orchestrating productive CD4 T-cell responses are well documented, the contraction of antigen (Ag)-specific CD4 T-cell populations following the resolution of primary immune response is however not molecularly understood. It has been demonstrated that a negative feedback loop can regulate CD4 T cell proliferation through direct T-T interactions, leading to the preferential exclusion of Ag-experienced T cells. This T cell intrinsic mechanism limits the expansion of effector CD4 T cells and may then interfere with therapeutic vaccine efficacy. Using Cas9-(constitutive/inducible)-expressing Dby-reactive T cells (from a TCR Transgenic RAG-/- mouse strain named Marilyn) coupled to a sgRNA library and an in vivo selection strategy, we will extensively identify the negative regulators of CD4 T cells migration and priming in an ongoing primary immune response. As a proof of concept, we will first inactivate candidate genes (already known to be involved in CD4 T cells negative regulation: TGF-b receptor,IFN-γ receptor, PD-1 and PD-L1) in Ag-experienced memory CD4 T cells, which will be enriched for their proliferative capacity in vivo and used as a second cohort in immunized mice. Then, we will develop a genome-wide screen approach to generate a library of knockout Ag-experienced T cells as a second cohort. We expect that further insight into CD4 suppressive mechanisms, which dampen efficient antitumor immune responses, will allow optimization of cancer immunotherapy.
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.
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2016
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75231 Paris
France
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.