title: IL-6 trans-signaling-dependent rapid development of cytotoxic CD8+ T cell function.
abstract: Immune control of infections with viruses or intracellular bacteria relies on cytotoxic CD8(+) T cells that use granzyme B (GzmB) for elimination of infected cells. During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Here, we report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hr. Such rapid acquisition of effector T cell function occurred through cross-presenting liver sinusoidal endothelial cells (LSECs) in the absence of innate immune stimulation and known costimulatory signaling. Rather, interleukin-6 (IL-6) trans-signaling was required and sufficient for rapid induction of GzmB expression in CD8(+) T cells. Such LSEC-stimulated GzmB-expressing CD8(+) T cells further responded to inflammatory cytokines, eliciting increased and protracted effector functions. Our findings identify a role for IL-6 trans-signaling in rapid generation of effector function in CD8(+) T cells that may be beneficial for vaccination strategies.
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Böttcher
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schanz
authors.affiliation: Institute of Biochemistry, Universität Kiel, Kiel 24098, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Garbers
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Zaremba
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Hegenbarth
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.affiliation: Genomics and Immunoregulation, LIMES Institute, University of Bonn, Bonn 53115, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.affiliation: Genomics and Immunoregulation, LIMES Institute, University of Bonn, Bonn 53115, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kastenmüller
authors.affiliation: Institute of Biochemistry, Universität Kiel, Kiel 24098, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn 53105, Germany; Institute of Molecular Immunology, Technische Universität München, München 81675, Germany. Electronic address: percy.knolle@tum.de.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D053804:Granzymes