Molecular cloning and functional characterization of guinea pig IL-12

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.