A NOVEL COSTIMULATORY FACTOR FOR GAMMA-INTERFERON INDUCTION FOUND IN THE LIVERS OF MICE CAUSES ENDOTOXIC-SHOCK

Administration of monoclonal anti-CD3 antibody to mice treated with Pr opionibacterium acnes induced secretion of a high level of gamma inter feron (IFN-gamma) into the circulation system, while it induced no sig nificant release in untreated mice. In order to analyze this high-leve l induction of IFN-gamma in these bacterium-treated mice,,ve investiga ted the factors that might be involved. An activity that induces IFN-g amma in T cells was observed in the liver extracts of mice treated wit h P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-gamma-inducing factor from the liver extract to hom ogeneity and characterized it. Its molecular mass was 18 to 19 kDa, an d its pI was 4.9. The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonst rated in the serum factor that was previously reported to have an IFN- gamma-inducing activity and to have an apparent molecular mass of 75 k Da. Moreover, the activity of this serum factor was recovered in the f raction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as th at of the factor from the liver extract. In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activiti es were apparently similar to those of interleukin-12. These results i ndicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated in vivo in re sponse to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P. acnes-treated mice.