Abstract
Following recognition of the cognate antigen, naïve T cells differentiate in a diverse progeny of memory T cells which differ at the phenotypic, gene expression and metabolic level. These molecular differences are at the basis of discrete functionality, migratory capacity and persistence in the long-term. Such a division of labor benefits adoptive T cell transfer immunotherapy approaches for cancer and viral infections, as increased persistence and effector functions in vivo result in better control of the disease. Preclinical data suggest that early-differentiated T memory stem cells are the most powerful anti-tumor T cell population following adoptive transfer, but their paucity ex vivo limits translation to the clinic. Here, we describe a simple protocol to derive large numbers of T memory stem cell and effector CD8+ T cell subsets from highly-purified CD8+ naïve T cell precursors. The obtained cells can be studied in vitro to understand the molecular basis of human memory T cell differentiation, or, when redirected with T cell receptor or chimeric antigen receptor, potentially used in vivo to favour T cell reconstitution or to treat established tumors or chronic infections.
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Acknowledgments
The authors wish to thank the members of the Laboratory of Translational Immunology for critical discussion. This work was supported by grants from the Fondazione Cariplo (Grant Ricerca Biomedica 2012/0683), the Italian Ministry of Health (Bando Giovani Ricercatori GR-2011-02347324) and the European Union Marie Curie Career Integration Grant 322093 (all to E.L.). E.L. is an International Society for the Advancement of Cytometry (ISAC) Marylou Ingram scholar. V.Z. is a student of the PhD program at the University of Milan, Italy.
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Zanon, V., Lugli, E. (2017). Differentiation of Diverse Progenies of Memory T Cells from Naïve CD8+ T Cell Precursors. In: Lugli, E. (eds) T-Cell Differentiation. Methods in Molecular Biology, vol 1514. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6548-9_8
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DOI: https://doi.org/10.1007/978-1-4939-6548-9_8
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