       Document 0538
 DOCN  M9620538
 TI    Mucosal adjuvant effect of cholera toxin in mice results from induction
       of T helper 2 (Th2) cells and IL-4.
 DT    9602
 AU    Marinaro M; Staats HF; Hiroi T; Jackson RJ; Coste M; Boyaka PN; Okahashi
       N; Yamamoto M; Kiyono H; Bluethmann H; et al; Department of
       Microbiology, University of Alabama at Birmingham; 35294, USA.
 SO    J Immunol. 1995 Nov 15;155(10):4621-9. Unique Identifier : AIDSLINE
       MED/96062277
 AB    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.
 DE    *Adjuvants, Immunologic  Administration, Oral  Animal  Antibody
       Formation  Cholera Toxin/*IMMUNOLOGY/PHARMACOLOGY  *Immunity, Mucosal
       Immunoglobulins/ANALYSIS  Interleukin-4/*IMMUNOLOGY  Lymphocyte
       Transformation/DRUG EFFECTS  Mice  Mice, Inbred C57BL  Mice, Knockout
       Muramidase/IMMUNOLOGY  Ovum/IMMUNOLOGY  Support, U.S. Gov't, P.H.S.
       Tetanus Toxoid/IMMUNOLOGY/PHARMACOLOGY  Th2 Cells/*IMMUNOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

