@article {542836,
	title = {Costimulation by B7-1 and B7-2 is required for autoimmune disease in MRL-Faslpr mice.},
	journal = {J Immunol},
	volume = {164},
	number = {11},
	year = {2000},
	month = {2000 Jun 1},
	pages = {6046-56},
	abstract = {Autoimmune lupus nephritis is dependent on infiltrating autoreactive leukocytes and Igs. B7 costimulatory molecules (B7-1 and B7-2) provide signals essential for T cell activation and Ig class switching. In MRL-Faslpr mice, a model of human lupus, although multiple tissues are targeted for autoimmune injury, nephritis is fatal. We identified intrarenal B7-1 and B7-2 expression, restricted to kidney-infiltrating leukocytes, before and increasing with progressive nephritis in MRL-Faslpr mice. Thus, we hypothesized that the B7 pathway is required for autoimmune disease in MRL-Faslpr mice. To investigate the role of B7 costimulatory molecules in this autoimmune disease, we generated a MRL-Faslpr strain deficient in B7-1 and B7-2. Strikingly, MRL-Faslpr mice lacking both B7 costimulators do not develop kidney (glomerular, tubular, interstitial, vascular) pathology, or proteinuria, and survive far longer. Intrarenal downstream effector transcripts (IFN-gamma, IL-12, monocyte chemoattractant protein-1, CSF-1) linked to nephritis remained at normal levels compared with wild-type mice. Skin lesions and lymphoid enlargement characteristic of MRL-Faslpr mice were diminished in B7-1/B7-2-deficient MRL-Faslpr mice. B7-1/B7-2-deficient MRL-Faslpr mice did not develop leukocytic infiltrates, elevated serum IgG and isotypes (G1,G2b,G3), autoantibodies, and intrarenal IgG deposits. Our findings demonstrate that B7-1 and B7-2 costimulatory pathways are critical to the pathogenesis of autoimmune lupus.},
	keywords = {Animals, Antibodies, Antinuclear, Antigens, CD, Antigens, CD80, Antigens, CD86, Autoimmune Diseases, Cell Movement, Chemokines, Cytokines, Disease Progression, Immunoglobulin G, Kidney Glomerulus, Leukocytes, Lung, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Mice, Knockout, Nephritis, Proteinuria, Species Specificity, Survival Analysis, Up-Regulation},
	issn = {0022-1767},
	author = {Kinoshita, K and Tesch, G and Schwarting, A and Maron, R and Sharpe, A. H. and Kelley, V R}
}
