IFN-γ production by intrinsic renal cells and bone marrow-derived cells is required for full expression of crescentic glomerulonephritis in mice

The contribution of IFN-γ from bone marrow (BM) and non-BM-derived cells to glomerular and cutaneous delayed-type hypersensitivity (DTH) was studied in mice. Chimeric IFN-γ mice (IFN-γ^+/+ BM chimera), in which IFN-γ production was restricted to BM-derived cells, were created by transplanting normal C57BL/6 (wild-type (WT)) BM into irradiated IFN-γ-deficient mice. BM IFN-γ-deficient chimeric mice (IFN-γ^-/- BM chimera) were created by transplanting WT mice with IFN-γ-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-γ-deficient mice showed significant protection from crescentic GN and reduced cutaneous DTH. IFN-γ^+/+ BM chimeric and IFN-γ^-/- BM chimeric mice showed similar attenuation of crescentic GN as IFN-γ-deficient mice, whereas cutaneous DTH was reduced only in IFN-γ^-/- BM chimeras. In crescentic GN, IFN-γ 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-γ^+/+ BM chimeric mice and was more severely reduced in IFN-γ-deficient mice and IFN-γ^-/- BM chimeric mice. These studies show that IFN-γ expression by both BM-derived cells and intrinsic renal cells is required for the development of crescentic GN, but IFN-γ production by resident cells is not essential for the development of cutaneous DTH.