title: Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny.
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 Bcl2 and Mki67 as a marker combination that enables the tracking of nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population size evolution to test potential progeny links and demonstrate that most cells follow a linear naive→early effector→late effector→memory pathway. Moreover, our mathematical model allows 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 their genealogy and to predict the outcome of immunization regimens in terms of memory cell numbers generated.
authors.affiliation: Team Dracula, Inria, 69603 Villeurbanne, France; Institut Camille Jordan, Université de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5208, 43 Boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Crauste
authors.affiliation: CIRI, ICL, INSERM U1111, Université Claude Bernard Lyon 1, CNRS UMR 5308, École Normale Supérieure de Lyon, Université de Lyon, 69007 Lyon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Mafille
authors.affiliation: CIRI, ICL, INSERM U1111, Université Claude Bernard Lyon 1, CNRS UMR 5308, École Normale Supérieure de Lyon, Université de Lyon, 69007 Lyon, France.
authors.forename: Lilia
authors.initials: L
authors.lastname: Boucinha
authors.affiliation: CIRI, ICL, INSERM U1111, Université Claude Bernard Lyon 1, CNRS UMR 5308, École Normale Supérieure de Lyon, Université de Lyon, 69007 Lyon, France.
authors.forename: Sophia
authors.initials: S
authors.lastname: Djebali
authors.affiliation: Team Dracula, Inria, 69603 Villeurbanne, France; Laboratory of Biology and Modelling of the Cell, Université de Lyon, ENS de Lyon, Université Claude Bernard, CNRS UMR 5239, INSERM U1210, 46 allée d'Italie Site Jacques Monod, 69007 Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gandrillon
authors.affiliation: CIRI, ICL, INSERM U1111, Université Claude Bernard Lyon 1, CNRS UMR 5308, École Normale Supérieure de Lyon, Université de Lyon, 69007 Lyon, France. Electronic address: jacqueline.marvel@inserm.fr.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
authors.affiliation: CIRI, ICL, INSERM U1111, Université Claude Bernard Lyon 1, CNRS UMR 5308, École Normale Supérieure de Lyon, Université de Lyon, 69007 Lyon, France. Electronic address: christophe.arpin@inserm.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Arpin
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000145:classification; D064229:Biological Ontologies; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D007156:Immunologic Memory / Q000276:immunology*; D019394:Ki-67 Antigen / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008962:Models, Theoretical; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2
chemical_list: D019394:Ki-67 Antigen; C000628856:MKI67 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: CD8 T cell differentiation; CD8 memory T cell ontogeny; differential equations; dynamical modeling; predictive tool; vaccine design