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*
Departments of Microbiology and Oral Biology, Immunobiology Vaccine Center, University of Alabama Medical Center, Birmingham, AL 35294;
Department of Internal Medicine, Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267;
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and
§
Departimento di Clinica Medica, Immunologia e Malattie Infettive, Universita Degli Studi di Bari, Bari, Italy
We have investigated the effects of IL-12 and cholera toxin (CT) on
the immune response to tetanus toxoid (TT) given by intranasal or oral
routes. CT inhibited IL-12-induced IFN-
secretion both in vivo and
in vitro. Intranasal administration of IL-12 to mice nasally immunized
with the combined vaccine of TT and CT resulted in increased
TT-specific IgG2a and IgG3 Abs, while IgG1 and IgE Ab responses were
markedly reduced. This shift of the CT-induced immune response toward
Th1 type was associated with TT-specific CD4+ T cells
secreting IFN- and reduced levels of Th2-type cytokines (i.e., IL-4,
IL-5, IL-6, and IL-10). In contrast, intranasal IL-12 enhanced the
CT-induced serum IgG1 and IgE Ab responses in mice given the combined
vaccine orally. IFN- secretion by TT-specific CD4+ T
cells was also enhanced; however, Th2-type cytokine responses were
predominant. Mucosal secretory IgA responses to oral or nasal vaccines
were not affected by intranasal IL-12. Thus, intranasal IL-12 delivery
influences Th cell subset development in mucosal inductive sites that
are dependent on the route of vaccine delivery.
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