IL-23 induces stronger sustained CTL and Th1 immune responses than IL-12 in hepatitis C virus envelope protein 2 DNA immunization.
IL-23 is a heterodimeric cytokine consisting of p19 and the p40 subunit of IL-12. IL-23 has been shown to possess IL-12-like biological activities, but is different in its capacity to stimulate memory T cells in vitro. In this study, we investigated whether IL-23 could influence envelope protein 2 (E2)-specific cell-mediated immunity induced by immunization of hepatitis C virus E2 DNA. We found that IL-23 induced long-lasting Th1 and CTL immune responses to E2, which are much stronger than IL-12-mediated immune responses. Interestingly, IL-23N220L, an N-glycosylation mutant showing reduced expression of excess p40 without changing the level of IL-23, exhibited a higher ratio of IFN-gamma- to IL-4-producing CD4(+) T cell frequency than did wild-type IL-23, suggesting a negative regulatory effect of p40 on Th1-prone immune response induced by IL-23. These data suggest that IL-23, particularly IL-23N220L, would be an effective adjuvant of DNA vaccine for the induction of durable Ag-specific T cell immunity.
Ha
Sang-Jun
SJ
National Research Laboratory of DNA Medicine, Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31 Hyoja-dong, Nam-gu, Pohang 790-784, Republic of Korea.
Kim
Doo-Jin
DJ
Baek
Kwan-Hyuck
KH
Yun
Yung-Dae
YD
Sung
Young-Chul
YC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007273:Injections, Intramuscular; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D018417:Th1 Cells / Q000276:immunology* / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; C508840:IL23A protein, human; C508841:Il23a protein, mouse; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D021122:Protein Subunits; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D018664:Interleukin-12