IL-12 is an effective adjuvant for induction of mucosal immunity.
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.
Boyaka
P N
PN
Department of Microbiology, The Immunobiology Vaccine Center, University of Alabama Medical Center, Birmingham 35294-2170, USA.
Marinaro
M
M
Jackson
R J
RJ
Menon
S
S
Kiyono
H
H
Jirillo
E
E
McGhee
J R
JR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D018928:Immunity, Mucosal / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology*; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control; D013744:Tetanus Toxin / Q000008:administration & dosage; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D015850:Interleukin-6; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; D018664:Interleukin-12