IL-12 Is an Effective Adjuvant for Induction of Mucosal Immunity

• Published in: The Journal of immunology (1950) 1999-01, Vol.162 (1), p.122-128
• Main Authors: Boyaka, Prosper N, Marinaro, Mariarosaria, Jackson, Raymond J, Menon, Satish, Kiyono, Hiroshi, Jirillo, Emilio, McGhee, Jerry R
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - therapeutic use; Administration, Intranasal; Animals; Antibodies, Bacterial - biosynthesis; CD4-Positive T-Lymphocytes - metabolism; Cytokines - biosynthesis; Immunity, Mucosal - immunology; Immunoglobulin A, Secretory - biosynthesis; Interleukin-12 - administration & dosage; Interleukin-12 - immunology; Interleukin-12 - therapeutic use; Interleukin-6 - administration & dosage; Mice; Mice, Inbred C57BL; Nasal Mucosa - immunology; Tetanus - immunology; Tetanus - prevention & control; Tetanus Toxin - administration & dosage; Tetanus Toxoid - administration & dosage; Tetanus Toxoid - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.1.122

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-gamma, 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.