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International Immunology, Vol. 13, No. 9, 1129-1139, September 2001
© 2001 Japanese Society for Immunology

Molecular cloning and functional characterization of guinea pig IL-12

Ikuo Shiratori12, Misako Matsumoto1, Shoutaro Tsuji1, Midori Nomura1, Kumao Toyoshima1 and Tsukasa Seya12

1 Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan
2 Department of Molecular Immunology, Nara Institute of Science and Technology, Ikoma, Nara 631-0101, Japan

Correspondence to: T. Seya, Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan

IL-12 is a heterodimeric cytokine that plays a central role in cell-mediated immunity. We cloned complete cDNAs of guinea pig homologues of IL-12 p35 and p40 subunits, and compared their functional properties with human IL-12. Both p35 and p40 mRNA were constitutively expressed in the testis and peritoneal macrophages. On immunoblotting, anti-guinea pig p40 antibody detected the constitutive expression of p40 protein in the testis, while in macrophages it was induced in response to lipopolysaccharide. An unidentified 200-kDa macromolecule was also expressed in the testis. All recombinant hybrid heterodimer p70 (guinea pig p70, human p70 and two interspecies heterodimers) exerted proliferative activity toward concanavalin A-primed guinea pig and human lymphoblasts in a dose-dependent manner. A similar tendency was observed in IFN-{gamma} production in IL-2-treated human lymphocytes. All hybrid heterodimers also induced IFN-{gamma} mRNA from IL-2-treated guinea pig splenocytes. Thus, unlike the current concept that the p35 subunit determines the species incompatibility of IL-12 in humans and mice, p35 has marginal ability to define its species-specific functional expression between humans and guinea pigs. In addition, constitutive expression of IL-12 or related molecules in the testis indicated a potential role of this molecule in regulation of physiological or pathophysiological conditions in the reproductive system.

Keywords: comparative immunology, cytokines, guinea pigs

Transmitting editor: L. L. Lanier


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