SJL and NOD macrophages are uniquely characterized by genetically programmed, elevated expression of the IL-12(p40) gene, suggesting a conserved pathway for the induction of organ-specific autoimmunity

Genetic susceptibility of the SJL mouse to experimental autoimmune encephal omyelitis (EAE) appears, inn part, to be a result of genes that promote abn ormal development of the pathogenic Type 1 (Th1) phenotype of neuroantigen- specific T-cells, Because antigen-presenting/accessory cells (APCs) produce cytokines that call modulate the development of Th1 and Th2 phenotypes, Te e addressed whether APCs front SJL mice were genetically programmed for ele vated expression of the Th1-promoting cytokine, IL-12, Activated peritoneal macrophages (M phi; i.e., APC) front naive SJL mice produced levels of TNF -alpha, IL-1, IL-6, IL-10, and TGF-beta within the range of six normal stra ins. In contrast, SJL IL-12p40 (in addition to IL-12p70) production was con sistently five- to 20-fold greater than that of any normal strain tested, w hich arose from elevated expression of the IL-12p40 but not the IL-12p35 ge ne, because p40 mRNA levels were eight- to 15-fold greater than those of no rmal strains. This aberrancy in IL-12p40 expression appears identical to th at observed in the NOD mouse, another strain prone to organ-specific autoim munity. A genetically programmed bias toward elevated expression of IL-12 i n M phi from the SJL and NOD strains of autoimmunity provides conserved mec hanism for the dominant Th1 development of naive, autoantigen-specific T-ce lls in strains, This study is the first demonstration a genetically program med aberrant phenotype is intrinsically expressed within a cell type in SJL mouse and provides insight into its predisposition for EAE.