Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+ T cell responses against a HBV DNA vaccine in mice.
Interleukin-22 (IL-22) is mainly produced by activated Th1 cells, Th17 cells and NK cells and promotes anti-microbial defense, pro-inflammatory and tissue remodeling responses. However, its potential use as a vaccine adjuvant has not been tested. In this study, we tested if a DNA construct expressing IL-22 (pVAX-IL-22) could be used as a molecular adjuvant to enhance host immune responses induced by HBV DNA vaccination (pcD-S2). After immunizing mice with pcD-S2 combined with pVAX-IL-22, we didn't find enhancement of HBsAg-specific antibody responses in comparison to mice immunized with pcD-S2 alone. However, there was an enhancement of the level of IL-17 expression in antigen specific CD8(+) cytotoxic T lymphocytes (Tc17). By using CD8 T-cell knockout (KO) and IL-17 KO mice, Tc17 cells were found to be a dominant population driving cytotoxicity. Importantly, there was a correlation between pVAX-IL-22 enhancement of T lymphocytes and a reduction of HBsAg-positive hepatocytes in HBsAg transgenic mice. These results demonstrate that IL-22 might be used as an effective adjuvant to enhance cellular immune responses during HBsAg DNA vaccination since it can induce Tc17 cells to break tolerance in HBsAg transgenic mice.
State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, P.R. China.
Bing
B
Wu
State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, P.R. China.
Qiang
Q
Zou
College of Veterinary Medicine; China Agricultural University; Beijing, P.R. China.
Yanxin
Y
Hu
State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, P.R. China; Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College; Shanghai, P.R. China.
Bin
B
Wang
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000097043:Interleukin-22
D000276:Adjuvants, Immunologic; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D020381:Interleukin-17; D007378:Interleukins; D019444:Vaccines, DNA; D000097043:Interleukin-22
DNA vaccine; HBV; IL-22; Tc17; adjuvant