Timoshanko Jennifer R, Holdsworth Stephen R, Kitching A Richard, Tipping Peter G
Center for Inflammatory Diseases, Monash University, and Department of Medicine, Monash Medical Center, Clayton, Victoria, Australia.
J Immunol. 2002 Apr 15;168(8):4135-41. doi: 10.4049/jimmunol.168.8.4135.
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.
在小鼠中研究了来自骨髓（BM）和非BM来源细胞的γ干扰素对肾小球和皮肤迟发型超敏反应（DTH）的作用。通过将正常C57BL/6（野生型（WT））骨髓移植到经照射的γ干扰素缺陷小鼠中，创建了嵌合γ干扰素小鼠（γ干扰素（+/+）BM嵌合体），其中γ干扰素的产生仅限于BM来源的细胞。通过将野生型小鼠与γ干扰素缺陷的骨髓进行移植，创建了BMγ干扰素缺陷嵌合小鼠（γ干扰素（-/-）BM嵌合体）。野生型和假嵌合小鼠（移植了野生型骨髓的野生型小鼠）在肾小球植入抗原后出现具有DTH特征的新月形肾小球肾炎（GN）（包括肾小球T细胞和巨噬细胞浸润），皮下抗原攻击后出现皮肤DTH。γ干扰素缺陷小鼠对新月形GN有显著的保护作用，皮肤DTH减轻。γ干扰素（+/+）BM嵌合小鼠和γ干扰素（-/-）BM嵌合小鼠与γ干扰素缺陷小鼠一样，新月形GN的减轻程度相似，而皮肤DTH仅在γ干扰素（-/-）BM嵌合体中降低。在新月形GN中，γ干扰素由肾小管细胞和偶尔的肾小球细胞表达，并与浸润的CD8（+）T细胞共定位，但不与CD4（+）T细胞或巨噬细胞共定位。在γ干扰素（+/+）BM嵌合小鼠中，肾MHC II类表达降低，在γ干扰素缺陷小鼠和γ干扰素（-/-）BM嵌合小鼠中降低更严重。这些研究表明，BM来源的细胞和肾固有细胞表达γ干扰素是新月形GN发生所必需的，但驻留细胞产生γ干扰素对皮肤DTH的发生不是必需的。
