Objective
The ability of adoptively-transferred T cells to mediate an immune response is modulated by the host environment. It has previously been shown that donor T cells proliferate and acquire memory-like characteristics when injected into lymphopenic hosts while in hosts with a « full » T cell compartment, they remain naïve and do not acquire effector function. As it is important to optimize the persistence and responsiveness of transferred T cells for immunotherapy strategies, we assessed whether T cell fate is dependent upon the conditioning regimen used to achieve lymphopenia. We induced lymphopenia in C57Bl/6 mice by sub-lethal irradiation or chemotherapy using busulfan with cyclophosphamide (Bu/Cy) and found that the relative engraftment of CD4 and CD8 T cells was markedly changed by the conditioning protocol: Irradiation-induced lymphopenia resulted in a skewed proliferation of donor CD8 T cells with a CD4:CD8 ratio of <1:5 whereas Bu/Cy-induced lymphopenia resulted in a massive proliferation of donor CD4 T cells with only minimal proliferation of CD8 T cells. These results clearly demonstrate that lymphopenic conditions are not equivalent in their potential to foster the regeneration of T cell pools. I propose to study the characteristics of the host and adoptively-transferred T cells generated in these two lymphopenic environments, with specific assessment of TH1, TH17 and Treg subsets. As the host microenvironment modulates T cell persistence and function, the effects of these regimens on the fate of stromal cell and APC populations will also be monitored. Moreover, I will study the consequences of irradiation and Bu/Cy conditioning on the reconstitution and function of adoptively-transferred T cells harboring a re-directed tumor-specific TCR in mice harbouring B cell lymphomas. The identification of parameters that enhance the survival and reactivity of adoptively-transferred tumor-specific T cells is important for the development of immunotherapy strategies
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 immunotherapy
- medical and health sciences basic medicine physiology homeostasis
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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.
FP7-PEOPLE-2009-RG
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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
75794 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.