title: Disparate individual fates compose robust CD8+ T cell immunity.
abstract: A core feature of protective T cell responses to infection is the robust expansion and diversification of naïve antigen-specific T cell populations into short-lived effector and long-lived memory subsets. By means of in vivo fate mapping, we found a striking variability of immune responses derived from individual CD8(+) T cells and show that robust acute and recall immunity requires the initial recruitment of multiple precursors. Unbiased mathematical modeling identifies the random integration of multiple differentiation and division events as the driving force behind this variability. Within this probabilistic framework, cell fate is specified along a linear developmental path that progresses from slowly proliferating long-lived to rapidly expanding short-lived subsets. These data provide insights into how complex biological systems implement stochastic processes to guarantee robust outcomes.
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich 81675, Germany.
authors.forename: Veit R
authors.initials: VR
authors.lastname: Buchholz
authors.forename: Michael
authors.initials: M
authors.lastname: Flossdorf
authors.forename: Inge
authors.initials: I
authors.lastname: Hensel
authors.forename: Lorenz
authors.initials: L
authors.lastname: Kretschmer
authors.forename: Bianca
authors.initials: B
authors.lastname: Weissbrich
authors.forename: Patricia
authors.initials: P
authors.lastname: Gräf
authors.forename: Admar
authors.initials: A
authors.lastname: Verschoor
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfer
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D060966:Clonal Selection, Antigen-Mediated; D003198:Computer Simulation; D007111:Immunity, Cellular; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D059010:Single-Cell Analysis; D013269:Stochastic Processes; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma