Molecular cloning and functional characterization of guinea pig IL-12

IL-12 is a heterodimeric cytokine that plays a central role in cell-mediate d immunity. We cloned complete cDNAs; of guinea pig homologues of IL-12 p35 and p40 subunits, and compared their functional properties with human IL-1 2. Both p35 and p40 mRNA were constitutively expressed in the testis and pe ritoneal macrophages. On immunoblotting, anti-guinea pig p40 antibody detec ted the constitutive expression of p40 protein in the testis, while in macr ophages it was induced in response to lipopolysaccharide. An unidentified 2 00-kDa macromolecule was also expressed in the testis. All recombinant hybr id heterodimer p70 (guinea pig p70, human p70 and two interspecies heterodi mers) exerted proliferative activity toward concanavalin A-primed guinea pi g and human lymphoblasts in a dose-dependent manner. A similar tendency was observed in IFN-gamma production in IL-2-treated human lymphocytes. All hy brid heterodimers also induced IFN-gamma mRNA from IL-2-treated guinea pig splenocytes. Thus, unlike the current concept that the p35 subunit determin es the species incompatibility of IL-12 in humans and mice, p35 has margina l ability to define its species-specific functional expression between huma ns and guinea pigs. In addition, constitutive expression of IL-12 or relate d molecules in the testis indicated a potential role of this molecule in re gulation of physiological or pathophysiological conditions in the reproduct ive system.