title: Influence of mucosal adjuvants on antigen passage and CD4+ T cell activation during the primary response to airborne allergen.
abstract: Ag delivery via the nasal route typically induces tolerance or fails to polarize CD4+ T cell responses unless an adjuvant is provided. To better understand this process, we assessed the effects of two mucosal adjuvants, Escherichia coli LPS and cholera toxin (CT), on Ag passage and T cell activation in the draining lymph nodes (DLN) of BALB/c mice following per nasal administration of the model protein allergen, OVA. We found a range of cell types acquired small amounts of fluorescent OVA in the DLN 4 h after per nasal administration. However, this early uptake was eclipsed by a wave of OVA+CD8alpha(low) dendritic cells that accumulated in the DLN over the next 20 h to become the dominant OVA-processing and -presenting population. Both LPS and CT stimulated increases in CD80 and CD86 expression on OVA+CD8alpha(low) DC. LPS also increased the number of OVA+CD8alpha(low) dendritic cells accumulating in the DLN. When the primary T cell response was examined after adoptive transfer of CD4+ T cells from DO11.10 mice, CT and LPS stimulated surprisingly similar effects on T cell activation and proliferation, IL-4 and IFN-gamma priming, and memory T cell production. Despite these similarities, T cell recipients immunized with CT, but not LPS, developed lung eosinophilia upon secondary OVA challenge. Thus, we found no bias within the DLN in Ag handling or the primary T cell response associated with the eventual Th2 polarization induced by CT, and suggest that additional tissue-specific factors influence the development of allergic disease in the airways.
authors.affiliation: Division of Cell Biology, Telethon Institute for Child Health Research, West Perth, WA 6872, Australia. mattw@ichr.uwa.edu.au
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Wikstrom
authors.forename: Eva
authors.initials: E
authors.lastname: Batanero
authors.forename: Miranda
authors.initials: M
authors.lastname: Smith
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Thomas
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis; D002772:Cholera Toxin / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D000941:Antigens; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D008070:Lipopolysaccharides; D010047:Ovalbumin; D002772:Cholera Toxin