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Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.

M Marinaro, H F Staats, T Hiroi, R J Jackson, M Coste, P N Boyaka, N Okahashi, M Yamamoto, H Kiyono, H Bluethmann, K Fujihashi and J R McGhee
J Immunol November 15, 1995, 155 (10) 4621-4629;
M Marinaro
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H F Staats
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T Hiroi
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R J Jackson
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M Coste
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P N Boyaka
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N Okahashi
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M Yamamoto
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H Kiyono
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H Bluethmann
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K Fujihashi
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J R McGhee
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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.

  • Copyright © 1995 by American Association of Immunologists

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The Journal of Immunology
Vol. 155, Issue 10
15 Nov 1995
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Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.
M Marinaro, H F Staats, T Hiroi, R J Jackson, M Coste, P N Boyaka, N Okahashi, M Yamamoto, H Kiyono, H Bluethmann, K Fujihashi, J R McGhee
The Journal of Immunology November 15, 1995, 155 (10) 4621-4629;

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Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.
M Marinaro, H F Staats, T Hiroi, R J Jackson, M Coste, P N Boyaka, N Okahashi, M Yamamoto, H Kiyono, H Bluethmann, K Fujihashi, J R McGhee
The Journal of Immunology November 15, 1995, 155 (10) 4621-4629;
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Print ISSN 0022-1767        Online ISSN 1550-6606