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

Fabien Crauste, Julien Mafille, Lilia Boucinha, Sophia Djebali, Olivier Gandrillon, Jacqueline Marvel, and Christophe Arpin (2017)

Cell Syst, 4(3):306-317.e4.

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 formalapproach based on mathematical models describing the dynamics of population sizeevolution to test potential progeny links and demonstrate that most cells followa linear naive-->early effector-->late effector-->memory pathway. Moreover, our mathematical model allows long-term prediction of memory cell numbers from a fewearly 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.

automatic medline import

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