title: Using bicistronic IL-4 reporter mice to identify IL-4 expressing cells following immunisation with aluminium adjuvant.
abstract: The Th2 dominated immune response induced by aluminium adjuvants remains a major limitation to their application to modern vaccines. Previous studies have shown that while these adjuvants can initiate Th2 responses in mice with disrupted IL-4 production or IL-4 signalling, a strong Th1 response becomes evident in these situations, suggesting that the main function of IL-4 in the response to aluminium adsorbed antigens is to antagonise Th1 induction. In this study we have employed the recently described, 4get reporter mice, that express GFP as part of a bicistronic IL-4-IRES-GFP mRNA, to identify IL-4 expressing cells in situ during an aluminium adjuvant-induced Th2 responses. These preliminary studies implicate conventional CD4+ T cells as the sole potential producers of IL-4 following immunisation with antigen prepared in aluminium adjuvants. Furthermore, as GFP positive cells are first detected in the lymph node, our studies indicate that these cells may act to block induction of Th1 responses by aluminium adjuvants. We conclude that devising strategies to block the effects of IL-4 production by these cells will facilitate the rational design of vaccine adjuvants that induce Th1 responses.
authors.affiliation: Division of Immunology, Infection & Inflammation, University of Glasgow, Glasgow G11 6NT, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: McDonald
authors.forename: Markus
authors.initials: M
authors.lastname: Mohrs
authors.forename: James
authors.initials: J
authors.lastname: Brewer
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000535:Aluminum / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007114:Immunization; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D010047:Ovalbumin; D000535:Aluminum