Disparate individual fates compose robust CD8+ T cell immunity

Veit R. Buchholz, Michael Flossdorf, Inge Hensel, Lorenz Kretschmer, Bianca Weissbrich, Patricia Gräf, Admar Verschoor, Matthias Schiemann, Thomas Höfer*, Dirk H. Busch

*Corresponding author for this work
    246 Citations (Scopus)

    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.

    Original languageEnglish
    JournalScience
    Volume340
    Issue number6132
    Pages (from-to)630-635
    Number of pages6
    ISSN0036-8075
    DOIs
    Publication statusPublished - 2013

    Research Areas and Centers

    • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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