title: Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming.
abstract: The function of dendritic cells (DCs) can be modulated through multiple signals, including recognition of pathogen-associated molecular patterns, as well as signals provided by rapidly activated leukocytes in the local environment, such as innate-like T cells. In this article, we addressed the possibility that the roles of different murine DC subsets in cross-priming CD8(+) T cells can change with the nature and timing of activatory stimuli. We show that CD8α(+) DCs play a critical role in cross-priming CD8(+) T cell responses to circulating proteins that enter the spleen in close temporal association with ligands for TLRs and/or compounds that activate NKT cells. However, if NKT cells are activated first, then CD8α(-) DCs become conditioned to respond more vigorously to TLR ligation, and if triggered directly, these cells can also contribute to priming of CD8(+) T cell responses. In fact, the initial activation of NKT cells can condition multiple DC subsets to respond more effectively to TLR ligation, with plasmacytoid DCs making more IFN-α and both CD8α(+) and CD8α(-) DCs manufacturing more IL-12. These results suggest that different DC subsets can contribute to T cell priming if provided appropriately phased activatory stimuli, an observation that could be factored into the design of more effective vaccines.
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand; School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand;
authors.forename: Taryn L
authors.initials: TL
authors.lastname: Osmond
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand;
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Farrand
authors.affiliation: The Ferrier Research Institute, Victoria University of Wellington, Lower Hutt 5010, New Zealand; and.
authors.forename: Gavin F
authors.initials: GF
authors.lastname: Painter
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551.
authors.forename: Christiane
authors.initials: C
authors.lastname: Ruedl
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand;
authors.forename: Troels R
authors.initials: TR
authors.lastname: Petersen
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6242, New Zealand; School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand; ihermans@malaghan.org.nz.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Hermans
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D037241:Mannose-Binding Lectins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D016898:Interferon-alpha; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D051193:Toll-Like Receptors; D018664:Interleukin-12