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Journal of Virology, September 2004, p. 9093-9104, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9093-9104.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Adjuvant Activities of Novel Cytokines, Interleukin-23 (IL-23) and IL-27, for Induction of Hepatitis C Virus-Specific Cytotoxic T Lymphocytes in HLA-A*0201 Transgenic Mice

Masanori Matsui,1* Osamu Moriya,1 Maria Laura Belladonna,2 Sadahiro Kamiya,3,4 François A. Lemonnier,5 Takayuki Yoshimoto,3 and Toshitaka Akatsuka1

Department of Microbiology, Saitama Medical School, Saitama,1 Intractable Immune System Disease Research Center,3 Department of Immunology, Tokyo Medical University, Tokyo, Japan,4 Department of Experimental Medicine, University of Perugia, Perugia, Italy,2 Department of AIDS and Retrovirus, Pasteur Institute, Paris, France5

Received 15 December 2003/ Accepted 19 April 2004

Searching the sequence databases has revealed two novel cytokines: interleukin-23 (IL-23) and IL-27. These cytokines are quite similar to, but clearly distinct from IL-12 in their structures and T-cell stimulatory fashions. In contrast to IL-12, however, little is known about the roles of IL-23 and IL-27 in the immune regulation. Previously, we evaluated the prime-boost immunization consisting of priming and the first boosting with the hepatitis C virus (HCV)-core expression plasmid, followed by a second boosting with recombinant adenovirus expressing HCV core for induction of HCV core-specific cytotoxic T lymphocytes (CTLs) in BALB/c mice. The present study demonstrates that HCV-specific CTL induction was greatly enhanced by coinoculation of an IL-12 expression plasmid in the prime-boost immunization, indicating the potent adjuvant activity of IL-12. We investigated whether similar adjuvant effects could be exerted by either IL-23 or IL-27 in a prime-boost immunization with HLA-A*0201 transgenic mice. Coadministration of either an IL-23 or an IL-27 expression plasmid, as well as an IL-12 expression plasmid, in a prime-boost immunization enhanced induction of HCV-specific CTLs and led to dramatic increases in the numbers of gamma interferon (IFN-{gamma})-producing, HCV-specific CD8+ cells. Further, preinjections of IL-12, IL-23, or IL-27 expression plasmids before immunization resulted in great increases in the number of IFN-{gamma}-producing, HCV-specific CD8+ cells in response to immunization with recombinant adenovirus. These data revealed that both IL-23 and IL-27, as well as IL-12, are potent adjuvants for epitope-specific CTL induction. The two novel cytokines might offer new prophylactic and therapeutic strategies against infectious pathogens such as HCV.

* Corresponding author. Mailing address: Department of Microbiology, Saitama Medical School, Moroyama-Cho, Iruma-Gun, Saitama 350-0495, Japan. Phone: 81-49-276-1166. Fax: 81-49-295-9107. E-mail: mmatsui{at}saitama-med.ac.jp.

Journal of Virology, September 2004, p. 9093-9104, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9093-9104.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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