title: Water-in-Oil-Only Adjuvants Selectively Promote T Follicular Helper Cell Polarization through a Type I IFN and IL-6-Dependent Pathway.
abstract: T follicular helper (Tfh) cells are a subset of CD4+T lymphocytes that promote the development of humoral immunity. Although the triggers required for the differentiation of the other major Th subsets are well defined, those responsible for Tfh cell responses are still poorly understood. We determined that mice immunized with peptide or protein Ags emulsified in IFA or related water-in-oil adjuvants develop a highly polarized response in which the majority of the Ag-specific CD4+T cells are germinal center-homing CXCR5+Bcl6+Tfh cells. Despite the absence of exogenous microbial pathogen-associated molecular patterns, the Tfh cell responses observed were dependent, in part, on MyD88. Importantly, in addition to IL-6, T cell-intrinsic type I IFN signaling is required for optimal Tfh cell polarization. These findings suggest that water-in-oil adjuvants promote Tfh cell-dominated responses by triggering endogenous alarm signals that, in turn, induce type I IFN-dependent differentiation pathway functioning in T cells.
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Nicolas
authors: 0000-0003-1306-6466
authors: N
authors: Riteau
authors: Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
authors: Andrea J
authors: AJ
authors: Radtke
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Kevin
authors: K
authors: Shenderov
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Lara
authors: 0000-0003-3558-0140
authors: L
authors: Mittereder
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Sandra D
authors: 0000-0002-6544-5268
authors: SD
authors: Oland
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Sara
authors: S
authors: Hieny
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors: Dragana
authors: D
authors: Jankovic
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and asher@niaid.nih.gov.
authors: Alan
authors: 0000-0001-7053-2895
authors: A
authors: Sher
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation; D018858:Germinal Center / Q000276:immunology; D056724:Immunity, Humoral; D007114:Immunization; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D009821:Oils; D010455:Peptides / Q000276:immunology; D054380:Receptors, CXCR5 / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014867:Water
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; C513179:CXCR5 protein, mouse; D007370:Interferon Type I; D015850:Interleukin-6; D009821:Oils; D010455:Peptides; D054380:Receptors, CXCR5; C577686:interleukin-6, mouse; D014867:Water