title: Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.
abstract: Despite pathophysiologic effects including diarrhea, cholera toxin (CT) is a potent mucosal immunogen and adjuvant. We investigated the influence of CT on T helper (Th)-type 1 (Th1) and Th2 cell-regulated Ag-specific B cell isotype and IgG subclass Ab responses elicited when the toxin was co-administered orally with different protein Ags. When mice were orally immunized with tetanus toxoid (TT) and CT as adjuvant, this regimen induced TT-specific secretory IgA responses in the gastrointestinal tract as well as serum IgG, including IgG1 and IgG2b subclasses, and IgA responses. This oral regimen also induced TT- and CT-B-specific IgE responses. In addition, CT also elicited adjuvant effects for Ag-specific IgG1, IgE, and IgA responses when two other protein Ags, OVA and hen egg white lysozyme, were given by the oral route. Quantitative reverse transcriptase-PCR was performed to assess levels of mRNA for Th1 (IFN-gamma) and Th2 (IL-4) cytokine expression in TT-stimulated CD4+ T cell cultures. Both Peyer's patches and splenic CD4+ T cells expressed markedly increased levels of IL-4-specific message, but did not result in changes in IFN-gamma mRNA expression. To determine whether the route of immunization influenced IgE responses, mice were immunized s.c. with TT and CT as adjuvant. Significant increases in total and TT-specific IgE Abs were induced when CT was co-administered. Taken together, these results show that CT acts as a mucosal adjuvant to enhance Th2-type responses and in particular, the IL-4 produced results in a characteristic Ab isotype pattern associated with this cytokine.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham 35294, USA.
authors.forename: M
authors.initials: M
authors.lastname: Marinaro
authors.forename: H F
authors.initials: HF
authors.lastname: Staats
authors.forename: T
authors.initials: T
authors.lastname: Hiroi
authors.forename: R J
authors.initials: RJ
authors.lastname: Jackson
authors.forename: M
authors.initials: M
authors.lastname: Coste
authors.forename: P N
authors.initials: PN
authors.lastname: Boyaka
authors.forename: N
authors.initials: N
authors.lastname: Okahashi
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
authors.forename: H
authors.initials: H
authors.lastname: Bluethmann
authors.forename: K
authors.initials: K
authors.lastname: Fujihashi
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D002772:Cholera Toxin / Q000276:immunology* / Q000494:pharmacology; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000032:analysis; D015847:Interleukin-4 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009113:Muramidase / Q000276:immunology; D010063:Ovum / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D013745:Tetanus Toxoid; D015847:Interleukin-4; D002772:Cholera Toxin; D009113:Muramidase