Section: New Results

Mathematical modeling of memory CD8 T cell ontogeny and quantitative predictions

Primary immune responses generate both short-term effector and long-term protective memory cells from naive CD8 T cells. The delineation of the genealogy linking those cell types has been complicated by the lack of molecular markers allowing to discriminate effector from memory cells at the peak of the response. Coupling transcriptomics and phenotypic analyses, and in collaboration with immunologists from Lyon (Jacqueline Marvel's team, Centre International de Recherche en Infectiologie), we identified a novel marker combination that allows to track nascent memory cells within the effector phase [13]. We then used mathematical models based upon our previous description of the dynamics of T cell immune response ( [35], [45]) to investigate potential differentiation pathways. We thereby could describe the dynamics of population-size evolutions to test potential progeny links and we could demonstrate that most cells follow a linear naive-early effector-late effector-memory pathway. Of interest for vaccine design, our mathematical model also allows long-term prediction of memory cell numbers from early experimental measurements. Alltogether, 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 (vaccines) in terms of memory cell numbers generated.