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The Journal of Immunology, 2004, 172: 525-531.
Copyright © 2004 by The American Association of Immunologists

IL-23 Induces Stronger Sustained CTL and Th1 Immune Responses Than IL-12 in Hepatitis C Virus Envelope Protein 2 DNA Immunization1

Sang-Jun Ha*, Doo-Jin Kim*, Kwan-Hyuck Baek*, Yung-Dae Yun{dagger} and Young-Chul Sung2,*

* National Research Laboratory of DNA Medicine, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea; and {dagger} Division of Molecular Life Science and Center for Cell Signaling Research, Ewha Woman’s University, Seoul, Korea

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.




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