title: CD11c depletion severely disrupts Th2 induction and development in vivo.
abstract: Although dendritic cells (DCs) are adept initiators of CD4(+) T cell responses, their fundamental importance in this regard in Th2 settings remains to be demonstrated. We have used CD11c-diphtheria toxin (DTx) receptor mice to deplete CD11c(+) cells during the priming stage of the CD4(+) Th2 response against the parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted CD11c(+) DCs from all tissues tested, with 70-80% efficacy. Even this incomplete depletion resulted in dramatically impaired CD4(+) T cell production of Th2 cytokines, altering the balance of the immune response and causing a shift toward IFN-γ production. In contrast, basophil depletion using Mar-1 antibody had no measurable effect on Th2 induction in this system. These data underline the vital role that CD11c(+) antigen-presenting cells can play in orchestrating Th2 development against helminth infection in vivo, a response that is ordinarily balanced so as to prevent the potentially damaging production of inflammatory cytokines.
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3JT Scotland, UK.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Phythian-Adams
authors.forename: Peter C
authors.initials: PC
authors.lastname: Cook
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Lundie
authors.forename: Lucy H
authors.initials: LH
authors.lastname: Jones
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Smith
authors.forename: Tom A
authors.initials: TA
authors.lastname: Barr
authors.forename: Kristin
authors.initials: K
authors.lastname: Hochweller
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Anderton
authors.forename: Günter J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001491:Basophils / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D047589:Leukocyte Reduction Procedures; D008213:Lymphocyte Activation; D051379:Mice; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma
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