Antigen availability determines CD8+ T cell-dendritic cell interaction kinetics and memory fate decisions

Sarah E. Henrickson, Mario Perro, Scott M. Loughhead, Balimkiz Senman, Susanne Stutte, Michael Quigley, Gabriela Alexe, Matteo Iannacone, Michael P. Flynn, Shaida Omid, Jonathan L. Jesneck, Sabrina Imam, Thorsten R. Mempel, Irina B. Mazo, W. Nicholas Haining, Ulrich H. Von Andrian

Research output: Contribution to journalArticle

Abstract

T cells are activated by antigen (Ag)-bearing dendritic cells (DCs) in lymph nodes in three phases. The duration of the initial phase of transient, serial DC-T cell interactions is inversely correlated with Ag dose. The second phase, characterized by stable DC-T cell contacts, is believed to be necessary for full-fledged Tcell activation. Here we have shown that this is not the case. CD8+ Tcells interacting with DCs presenting low-dose, short-lived Ag did not transition to phase 2, whereas higher Ag dose yielded phase 2 transition. Both antigenic constellations promoted Tcell proliferation and effector differentiation but yielded different transcriptome signatures at 12hr and 24hr. Tcells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, Tcells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with Tcell-DCs interaction kinetics.

Original languageEnglish
Pages (from-to)496-507
Number of pages12
JournalImmunity
Volume39
Issue number3
DOIs
Publication statusPublished - Sep 19 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    Henrickson, S. E., Perro, M., Loughhead, S. M., Senman, B., Stutte, S., Quigley, M., Alexe, G., Iannacone, M., Flynn, M. P., Omid, S., Jesneck, J. L., Imam, S., Mempel, T. R., Mazo, I. B., Haining, W. N., & Von Andrian, U. H. (2013). Antigen availability determines CD8+ T cell-dendritic cell interaction kinetics and memory fate decisions. Immunity, 39(3), 496-507. https://doi.org/10.1016/j.immuni.2013.08.034