IL-23 induces stronger sustained CTL and Th1 immune responses than IL-12 in hepatitis C virus envelope protein 2 DNA immunization |
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Authors: | Ha Sang-Jun Kim Doo-Jin Baek Kwan-Hyuck Yun Yung-Dae Sung Young-Chul |
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Affiliation: | 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. |
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Abstract: | 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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