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*
Departments of Microbiology and Oral Biology, The Immunobiology Vaccine Center, University of Alabama Medical Center, Birmingham, AL 35294;
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan;
DNAX Research Institute, Palo Alto, CA 94304; and
§
Departimento di Clinica Medica, Immunologia e Malattie Infetive, Universita Degli Studi di Bari, Bari, Italy
We addressed the effects of two cytokines, IL-6 and IL-12, derived
from APCs, for the development of mucosal IgA Ab responses following
their nasal delivery with the protein vaccine tetanus toxoid (TT). Mice
treated nasally with IL-6 and TT showed higher TT-specific serum IgG
(mainly IgG1 and IgG2b) Ab responses than did control mice, but
exhibited no IgE and negligible secretory IgA (S-IgA) Ab responses. In
contrast, IL-12 administered nasally with TT not only induced sharp
increases in TT-specific serum IgG (mainly IgG1 and IgG2b) and IgA, but
also elevated mucosal S-IgA Ab responses. Coadministration of IL-6 and
IL-12 with TT did not enhance the mucosal or serum Ab responses over
those seen with IL-12 alone. TT-specific CD4+ T cells from
mice given TT with IL-6 or IL-12 produced higher levels of IFN-
,
IL-6, and IL-10 than did those from control mice, but only negligible
levels of IL-4 and IL-5. In summary, both intranasal IL-6 and IL-12
induced serum Abs that protected mice from systemic challenge with TT,
whereas only IL-12 induced mucosal S-IgA Ab responses. The significance
of IL-12-induced Th1-type responses for regulation of both mucosal and
systemic immunity is discussed.
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