CLONING OF A NEW CYTOKINE THAT INDUCES IFN-GAMMA PRODUCTION BY T-CELLS

THE mechanism underlying the differentiation of CD4(+) T cells into fu nctionally distinct subsets (Th1 and Th2) is incompletely understood(1 -3), and hitherto unidentified cytokines may be required for the funct ional maturation of these cells(4). Here we report the cloning of a re cently identified IFN-gamma-inducing factor (IGIF) that augments natur al killer (NK) activity in spleen cells(5,6). The gene encodes a precu rsor protein of 192 amino acids and a mature protein of 157 amino acid s, which have no obvious similarities to any peptide in the databases. Messenger RNAs for IGIF and interleukin-12 (IL-12) are readily detect ed in Kupffer cells and activated macrophages. Recombinant IGIF induce s IFN-gamma more potently than does IL-12, apparently through a separa te pathway. Administration of anti-IGIF antibodies prevents liver dama ge in mice inoculated with Propionibacterium acnes and challenged with lipopolysaccharide, which induces toxic shock. IGIF may he involved i n the development of Th1 cells and also in mechanisms of tissue injury in inflammatory reactions.