Abstract
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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