title: Low-dose oral tolerance due to antigen in the diet suppresses differentially the cholera toxin-adjuvantized IgE, IgA and IgG response.
abstract: BACKGROUND
  Cholera toxin (CT) is used as a mucosal adjuvant amongst other applications for studying food allergy because oral administration of antigen with CT induces an antigen-specific type 2 response, including IgE and IgA production. Previously established oral tolerance due to antigen in the diet may radically impact on the CT-adjuvantized immune response. The present study served to evaluate the effect of previously established low-dose oral tolerance on the CT-adjuvantized immune response towards a food antigen.
  
  
  METHODS
  Mice fed a diet containing microgram levels of the soy protein Kunitz soy-trypsin inhibitor (KSTI) (F0 mice) and mice fed a soy-free diet (F2 mice) were orally immunized with KSTI and CT. KSTI-specific serum IgG1, IgG2a, IgA and IgE and fecal IgA were monitored. KSTI-stimulated cell proliferation and interleukin (IL)-6 production were determined.
  
  
  RESULTS
  The anti-KSTI IgE and IgA responses in the F0 mice were substantially suppressed, while the IgG1 and IgG2a responses were not suppressed after five oral immunizations. The response suppression tended to decline with increasing numbers of immunizations suggesting that the suppression could be overcome by multiple immunizations. However, cell proliferation and IL-6 production were clearly suppressed even after five immunizations.
  
  
  CONCLUSIONS
  Priorly established low-dose oral tolerance considerably suppressed the CT-adjuvantized KSTI-specific IgE, IgA and cellular immune response but only weakly and transiently the IgG response. The results revealed that low-dose oral tolerance includes the mucosal IgA response and that CT, albeit mediating an antigen-specific response, does not fully abrogate previously established oral tolerance.
authors.affiliation: BioCentrum-DTU, Biochemistry and Nutrition, Technical University of Denmark, Kgs Lyngby, Denmark. hrc@biocentrum.dtu.dk
authors.forename: Hanne R
authors.initials: HR
authors.lastname: Christensen
authors.forename: Tanja M R
authors.initials: TM
authors.lastname: Kjaer
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiaer
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D002772:Cholera Toxin / Q000276:immunology / Q000494:pharmacology*; D007108:Immune Tolerance; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D015850:Interleukin-6; D007073:Immunoglobulin E; D002772:Cholera Toxin; D014360:Trypsin Inhibitor, Kunitz Soybean