Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.
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.
Marinaro
M
M
Department of Microbiology, University of Alabama at Birmingham 35294, USA.
Staats
H F
HF
Hiroi
T
T
Jackson
R J
RJ
Coste
M
M
Boyaka
P N
PN
Okahashi
N
N
Yamamoto
M
M
Kiyono
H
H
Bluethmann
H
H
Fujihashi
K
K
McGhee
J R
JR
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*
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D013745:Tetanus Toxoid; D015847:Interleukin-4; D002772:Cholera Toxin; D009113:Muramidase