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Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny

Fabien Crauste 1 Julien Mafille 2, 3 Lilia Boucinha 2, 4 Sophia Djebali 2 Olivier Gandrillon 5, 1 Jacqueline Marvel 2 Christophe Arpin 2 
1 DRACULA - Multi-scale modelling of cell dynamics : application to hematopoiesis
CGPhiMC - Centre de génétique et de physiologie moléculaire et cellulaire, Inria Grenoble - Rhône-Alpes, ICJ - Institut Camille Jordan [Villeurbanne]
2 Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes
CIRI - Centre International de Recherche en Infectiologie - UMR
Abstract : Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector and memory cells has been complicated by the lack of phenotypes discriminating effector from memory differentiation stages. Using transcriptomics and phenotypic analyses, we identify a novel marker combination that allows us to track nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population-size evolutions to test potential progeny links and demonstrate that most cells follow a linear naive-early effector-late effector-memory pathway. Moreover, our mathematical modelallows long-term prediction of memory cell numbers from a few early experimental measurements. Our work thus provides a phenotypic means to identify effector and memory cells, as well as a mathematical framework to investigate the ontology of their generation and to predict the outcome of immunization regimens in terms of memory cell numbers generated.
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Submitted on : Wednesday, May 31, 2017 - 10:52:48 AM
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Fabien Crauste, Julien Mafille, Lilia Boucinha, Sophia Djebali, Olivier Gandrillon, et al.. Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny. Cell Systems, Elsevier, 2017, 4 (3), pp.306-317. ⟨10.1016/j.cels.2017.01.014⟩. ⟨hal-01409637⟩



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