IL-12 Deficiency in MRL-Fas Mice Delays Nephritis and Intrarenal IFN- Expression, and Diminishes Systemic Pathology

Autoimmune disease in MRL-Fas lpr mice is characterized by fatal nephritis, systemic pathology, and autoantibodies, mimicking human lupus. We previously reported that 1) intrarenal IL-12 elicits nephritis by fostering the accumulation of intrarenal IFN-␥-secreting T cells, and 2) MRL-Fas lpr mice deficient in the IFN-␥ receptor were spared from nephritis. Therefore, we hypothesized that eliminating IL-12 in MRL-Fas lpr mice reduces IFN-␥-secreting cells and thereby prevents systemic pathology. For this purpose, we constructed an IL-12p40-deficient MRL-Fas lpr (IL-12 ؊/؊) strain. We determined that glomerular and interstitial, but not perivascular, renal pathology were decreased in IL-12 ؊/؊ mice vs the wild-type (WT) strain (5 mo of age). Similarly, systemic pathology (lung, lacrimal and salivary glands, skin, and lymphadenopathy) was diminished. The intrarenal accumulation of T cells (CD4