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The Journal of Immunology, 2002, 168: 4135-4141.
Copyright © 2002 by The American Association of Immunologists

IFN-{gamma} Production by Intrinsic Renal Cells and Bone Marrow-Derived Cells Is Required for Full Expression of Crescentic Glomerulonephritis in Mice1

Jennifer R. Timoshanko, Stephen R. Holdsworth, A. Richard Kitching and Peter G. Tipping2

Center for Inflammatory Diseases, Monash University, and Department of Medicine, Monash Medical Center, Clayton, Victoria, Australia

The contribution of IFN-{gamma} from bone marrow (BM) and non-BM-derived cells to glomerular and cutaneous delayed-type hypersensitivity (DTH) was studied in mice. Chimeric IFN-{gamma} mice (IFN-{gamma}+/+ BM chimera), in which IFN-{gamma} production was restricted to BM-derived cells, were created by transplanting normal C57BL/6 (wild-type (WT)) BM into irradiated IFN-{gamma}-deficient mice. BM IFN-{gamma}-deficient chimeric mice (IFN-{gamma}-/- BM chimera) were created by transplanting WT mice with IFN-{gamma}-deficient BM. WT and sham chimeric mice (WT mice transplanted with WT BM) developed crescentic glomerulonephritis (GN) with features of DTH (including glomerular T cell and macrophage infiltration) in response to an Ag planted in their glomeruli and skin DTH following subdermal Ag challenge. IFN-{gamma}-deficient mice showed significant protection from crescentic GN and reduced cutaneous DTH. IFN-{gamma}+/+ BM chimeric and IFN-{gamma}-/- BM chimeric mice showed similar attenuation of crescentic GN as IFN-{gamma}-deficient mice, whereas cutaneous DTH was reduced only in IFN-{gamma}-/- BM chimeras. In crescentic GN, IFN-{gamma} was expressed by tubular cells and occasional glomerular cells and was colocalized with infiltrating CD8+ T cells, but not with CD4+ T cells or macrophages. Renal MHC class II expression was reduced in IFN-{gamma}+/+ BM chimeric mice and was more severely reduced in IFN-{gamma}-deficient mice and IFN-{gamma}-/- BM chimeric mice. These studies show that IFN-{gamma} expression by both BM-derived cells and intrinsic renal cells is required for the development of crescentic GN, but IFN-{gamma} production by resident cells is not essential for the development of cutaneous DTH.




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