title: Differentiation of Diverse Progenies of Memory T Cells from Naïve CD8+T Cell Precursors.
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.
authors: Laboratory of Translational Immunology, Humanitas Clinical and Research Center, Via Alessandro Manzoni 113, Rozzano, Milan, Italy.
authors: Veronica
authors: V
authors: Zanon
authors: Laboratory of Translational Immunology, Humanitas Clinical and Research Center, Via Alessandro Manzoni 113, Rozzano, Milan, Italy. enrico.lugli@humanitasresearch.it.
authors: Enrico
authors: E
authors: Lugli
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation / Q000379:methods*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D013234:Stem Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
keywords: Adoptive cell transfer; CD8+ T cells; Cancer; Cytokines; Effector T cells; Immunotherapy; Memory; Naïve; T memory stem cells; TCR stimulation