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1996-02-26
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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).