title: Dendritic cells and NK cells stimulate bystander T cell activation in response to TLR agonists through secretion of IFN-alpha beta and IFN-gamma.
abstract: Recognition of conserved features of infectious agents by innate pathogen receptors plays an important role in initiating the adaptive immune response. We have investigated early changes occurring among T cells after injection of TLR agonists into mice. Widespread, transient phenotypic activation of both naive and memory T cells was observed rapidly after injection of molecules acting through TLR3, -4, -7, and -9, but not TLR2. T cell activation was shown to be mediated by a combination of IFN-alphabeta, secreted by dendritic cells (DCs), and IFN-gamma, secreted by NK cells; notably, IFN-gamma-secreting NK cells expressed CD11c and copurified with DCs. Production of IFN-gamma by NK cells could be stimulated by DCs from TLR agonist-injected mice, and although soluble factors secreted by LPS-stimulated DCs were sufficient to induce IFN-gamma, maximal IFN-gamma production required both direct contact of NK cells with DCs and DC-secreted cytokines. In vitro, IFN-alphabeta, IL-18, and IL-12 all contributed to DC stimulation of NK cell IFN-gamma, whereas IFN-alphabeta was shown to be important for induction of T cell bystander activation and NK cell IFN-gamma production in vivo. The results delineate a pathway involving innate immune mediators through which TLR agonists trigger bystander activation of T cells.
authors.affiliation: The Edward Jenner Institute for Vaccine Research, Compton, Newbury, United Kingdom.
authors.forename: Arun T
authors.initials: AT
authors.lastname: Kamath
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Sheasby
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000276:immunology*; D039521:CD11c Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007370:Interferon Type I / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000819:agonists*; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D007370:Interferon Type I; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D007371:Interferon-gamma