Explore the words cloud of the CD4CRISPR project. It provides you a very rough idea of what is the project "CD4CRISPR" about.
The following table provides information about the project.
|Coordinator Country||France [FR]|
|Total cost||185˙076 €|
|EC max contribution||185˙076 € (100%)|
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
|Duration (year-month-day)||from 2017-04-01 to 2019-03-31|
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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.
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The information about "CD4CRISPR" are provided by the European Opendata Portal: CORDIS opendata.
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