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Content archived on 2024-06-16

THE GENERATION OF CD8 T CELL MEMORY

Objective

"CD8+ T cells are fundamental targets for improved vaccination strategies, since they are fundamental to virus and tumors control, and current immunization protocols to generate efficient CD8+ responses are essentially inadequate. Major handicaps are the l ack of correlation between the current tests used to study CD8+ T cell function and infection out-come or efficient memory generation. The present project will study responses and memory using new methodological advancements that should allow efficient cha racterization of CD8+ differentiation programs. Functional profiles will be defined using a new methodology developed in the host laboratory, that allows the simultaneous quantification of 20 relevant gene products expression in each individual antigen-spe cific CD8+ T cell ex-vivo. We will study the impact of different immunization protocols, studying the same clone of T cell receptor (TCR) transgenic (Tg) cells responding to the same antigen presented in different forms, i.e. cells expressing naturally th e antigen, mature and immature dendritic cells loaded ¿in vitro¿ with peptide or recombinant Listeria expressing the same antigen. To evaluate the impact of TCR affinity, we will also study the responses to the same immunization protocol of different T cel l clones, covering a large range of TCR affinities. Finally we will evaluate the role of IL-7R in memory T cell generation. We developed IL-7R Tg mice that cannot down regulate IL7R during immune responses. IL-7R expression is essential for peripheral T ce ll survival, but the reason for its down-regulation upon T cell activation and the mode of its re-expression in memory T cells is obscure. The study of immune responses in these Tg mice will provide definitive answers on the role IL-7R expression in CD8+ m emory generation. Moreover, together with 31 European laboratories associated into the EU network #512074 this study will allow a detailed genetic mapping of CD8+ memory cell differentiation."

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-7
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Funding Scheme

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IIF - Marie Curie actions-Incoming International Fellowships

Coordinator

UNIVERSITE RENE DESCARTES PARIS 5
EU contribution
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Address
DIVISION DE LA RECHERCHE 12 RUE DE L'ECOLE DE MEDECINE
PARIS
France

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Total cost

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