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From the * Departments of Microbiology and Oral Biology, The Immunobiology Vaccine Center, The
University of Alabama at Birmingham, Birmingham, Alabama 35294-2170; Our past studies have shown that the mucosal adjuvant cholera toxin (CT) induces T helper
type 2 (Th2) responses with systemic IgG1, IgE and mucosal secretory IgA (S-IgA) antibodies
(Abs). In this study, recombinant murine IL-12 (rmIL-12) was given either parenterally or
orally to mice orally immunized with tetanus toxoid (TT) and CT to determine whether this
cytokine could redirect the CT-induced Th2-type responses and what effect this shift would have on S-IgA Ab responses. Intraperitoneal administration of rmIL-12 shifted TT-specific responses toward Th1-type and resulted in CD4+ T cells producing IFN-
Department of
Internal Medicine, Division of Immunology, University of Cincinnati College of Medicine, Cincinnati,
Ohio 45267-0563; § Department of Mucosal Immunology, Research Institute for Microbial Diseases,
Osaka University, Suita, Osaka, Japan 565; and ¶ Department of Microbiology and Immunology,
University of Bari, Bari, Italy
and IL-2 with markedly reduced levels of Th2-type cytokines. This cytokine profile was accompanied by increased
delayed-type hypersensitivity (DTH) and shifts in serum IgG1 to IgG2a and IgG3 anti-TT Ab
responses. Further, serum IgE and S-IgA Ab responses were markedly reduced by parenteral
IL-12. When IL-12 complexed to liposomes was given orally both shifts to IgG2a and IgG3
and low IgE Abs again occurred concomitant with enhanced serum IFN-
and DTH responses. Interestingly, oral rmIL-12 did not result in significant levels of serum IL-12 nor altered S-IgA Ab responses and resulted in higher levels of some Th2-type cytokines both in
vitro and in vivo when compared with parenteral IL-12. Our results show that the shifts in systemic immune responses with intact S-IgA Abs which occur after oral delivery of IL-12-liposomes are due to cytokine effects in the Peyer's patches and suggest new strategies for the targeted manipulation of Th1- and Th2-type responses to mucosal vaccines.
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