title: Gr1+IL-4-producing innate cells are induced in response to Th2 stimuli and suppress Th1-dependent antibody responses.
abstract: Alum is used as a vaccine adjuvant and induces T(h)2 responses and T(h)2-driven antibody isotype production against co-injected antigens. Alum also promotes the appearance in the spleen of Gr1+IL-4+ innate cells that, via IL-4 production, induce MHC II-mediated signaling in B cells. To investigate whether these Gr1+ cells accumulate in the spleen in response to other T(h)2-inducing stimuli and to understand some of their functions, the effects of injection of alum and eggs from the helminth, Schistosoma mansoni, were compared. Like alum, schistosome eggs induced the appearance of Gr1+IL-4+ cells in spleen and promoted MHC II-mediated signaling in B cells. Unlike alum, however, schistosome eggs did not promote CD4 T cell responses against co-injected antigens, suggesting that the effects of alum or schistosome eggs on splenic B cells cannot by themselves explain the T cell adjuvant properties of alum. Accordingly, depletion of IL-4 or Gr1+ cells in alum-injected mice had no effect on the ability of alum to improve expansion of primary CD4 T cells. However, Gr1+ cells and IL-4 played some role in the effects of alum, since depletion of either resulted in antibody responses to antigen that included not only the normal T(h)2-driven isotypes, like IgG1, but also a T(h)1-driven isotype, IgG2c. These data suggest that alum affects the immune response in at least two ways: one, independent of Gr1+ cells and IL-4, that promotes CD4 T cell proliferation and another, via Gr1+IL-4+ cells, that participates in the polarization of the response.
authors.affiliation: Integrated Department of Immunology, National Jewish Medical and Research Center, Howard Hughes Medical Institute, 1400 Jackson Street, CO 80206, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: McKee
authors.forename: Megan
authors.initials: M
authors.lastname: MacLeod
authors.forename: Janice
authors.initials: J
authors.lastname: White
authors.forename: Frances
authors.initials: F
authors.lastname: Crawford
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.forename: Philippa
authors.initials: P
authors.lastname: Marrack
mesh_terms: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II; D007113:Immunity, Innate; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000947:Antigens, Helminth; C503133:Gr-1 protein, mouse; D007132:Immunoglobulin Isotypes; D019707:Receptors, Chemokine; D015847:Interleukin-4; C041524:aluminum sulfate; D010047:Ovalbumin