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 infl uence of CT on T helper (Th)-type 1 (Th1) and Th2 cell-regulated Ag-sp ecific 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 toroid (TT) and CT as adjuvant, th is regimen induced TT-specific secretory IgA responses in the gastroin testinal tract as well as serum IgG, including IgG1 and IgG2b subclass es, and IgA responses. This oral regimen also induced TT- and CT-B-spe cific IgE responses. In addition, CT also elicited adjuvant effects fo r Ag-specific IgG1, IgE, and IgA responses when two other protein Ags, OVA and hen egg white lysozyme, were given by the oral route. Quantit ative reverse transcriptase-PCR was performed to assess levels of mRNA for Th1 (IFN-gamma) and Th2 (IL-4) cytokine expression in TT-stimulat ed CD4(+) T cell cultures. Both Peyer's patches and splenic CD4(+) T c ells 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 to tal 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 res ults in a characteristic Ab isotype pattern associated with this cytok ine.