Antigen Availability Determines CD8+ T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions

• Published in: Immunity (Cambridge, Mass.) Mass.), 2013-09, Vol.39 (3), p.496-507
• Main Authors: Henrickson, Sarah E., Perro, Mario, Loughhead, Scott M., Senman, Balimkiz, Stutte, Susanne, Quigley, Michael, Alexe, Gabriela, Iannacone, Matteo, Flynn, Michael P., Omid, Shaida, Jesneck, Jonathan L., Imam, Sabrina, Mempel, Thorsten R., Mazo, Irina B., Haining, W. Nicholas, von Andrian, Ulrich H.
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antigen Presentation; Antigen-Presenting Cells - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Communication; Cell Differentiation; Dendritic Cells - immunology; Dendritic Cells - metabolism; Gene expression; Immunologic Memory - immunology; Immunology; Lymph Nodes - immunology; Lymphocyte Activation; Lymphocytes; Lymphocytic choriomeningitis virus - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Peptides; T cell receptors; Transcriptome - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.08.034

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 T cell activation. Here we have shown that this is not the case. CD8+ T cells 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 T cell proliferation and effector differentiation but yielded different transcriptome signatures at 12 hr and 24 hr. T cells that experienced phase 2 developed long-lived memory, whereas conditions without stable contacts yielded immunological amnesia. Thus, T cells make fate decisions within hours after Ag exposure, resulting in long-term memory or abortive effector responses, correlating with T cell-DCs interaction kinetics. [Display omitted] •Stable DC-CD8+ T cell contacts are not required for effector T cell differentiation•Memory differentiation of CD8+ T cells is correlated with stable DC-T cell contacts•Low- and high-dose antigen initiate distinct transcriptional programs in T cells•CD8+ T cells make a memory fate decision within 24 hr after antigen encounter