Chadban S J, Tesch G H, Foti R, Lan H Y, Atkins R C, Nikolic-Paterson D J
Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
Immunology. 1998 May;94(1):72-8. doi: 10.1046/j.1365-2567.1998.00487.x.
Inhibition of major histocompatibility complex (MHC) class II expression by macrophages is the primary mechanism by which interleukin-10 (IL-10) exerts immune suppression. Little, however, is known of the effects of IL-10 on other types of cells which can be induced to express MHC class II during an inflammatory response. We therefore studied the effects of IL-10 treatment on the expression of MHC class II molecules in a rat model of immunologically induced glomerulonephritis. MHC class II mRNA levels in whole kidney were increased in saline-treated (control) animals with glomerulonephritis (2.6-fold increase versus normal, P = 0.028) and this was partially inhibited by treatment with IL-10 (P = NS). Double immunostaining of tissue sections was used to compare MHC class II expression by infiltrating macrophages and resident glomerular cells. IL-10 treatment reduced the proportion of glomerular macrophages which expressed detectable MHC class II (70% reduction, P = 0.03). In contrast, IL-10 treatment was associated with an increase in the number of resident glomerular cells expressing MHC class II, particularly within mesangial areas. Therefore, the effects of IL-10 on macrophages and mesangial cells were compared in vitro. IL-10 reduced constitutive MHC class II mRNA and cell surface expression by peritoneal macrophages. In contrast, IFN-gamma-stimulated mesangial cells (1097 cell line) cultured with IL-10 for 24 hr showed increased MHC class II mRNA (26% increase) and surface expression (72% increase in percentage MHC II+ by flow cytometry, P = 0.04) as compared with cells stimulated with IFN-gamma alone. IL-10 also directly up-regulated expression of ICAM-1 by 1997 cells. In conclusion, IL-10 was found to have contrasting effects on the production and cell surface expression of MHC class II molecules by mesengial cells and by macrophages, both in vitro and in vivo. The implications of these findings for IL-10-mediated immunosuppression are discussed.
巨噬细胞对主要组织相容性复合体（MHC）II类分子表达的抑制作用是白细胞介素10（IL-10）发挥免疫抑制作用的主要机制。然而，关于IL-10对炎症反应期间可被诱导表达MHC II类分子的其他类型细胞的影响，人们所知甚少。因此，我们在免疫诱导的肾小球肾炎大鼠模型中研究了IL-10处理对MHC II类分子表达的影响。在患有肾小球肾炎的生理盐水处理（对照）动物中，全肾的MHC II类mRNA水平升高（与正常相比增加2.6倍，P = 0.028），而IL-10处理可部分抑制这种升高（P =无显著性差异）。使用组织切片的双重免疫染色来比较浸润巨噬细胞和肾小球固有细胞的MHC II类表达。IL-10处理降低了表达可检测到的MHC II类的肾小球巨噬细胞比例（降低70%，P = 0.03）。相反，IL-10处理与表达MHC II类的肾小球固有细胞数量增加有关，特别是在系膜区域内。因此，在体外比较了IL-10对巨噬细胞和系膜细胞的影响。IL-10降低了腹膜巨噬细胞组成性MHC II类mRNA和细胞表面表达。相反，与单独用γ干扰素刺激的细胞相比，用IL-10培养24小时的γ干扰素刺激的系膜细胞（1097细胞系）显示MHC II类mRNA增加（增加26%）和表面表达增加（通过流式细胞术检测，MHC II +百分比增加72%，P = 0.04）。IL-10还直接上调了1997细胞ICAM-1的表达。总之，发现IL-10在体外和体内对系膜细胞和巨噬细胞产生MHC II类分子以及细胞表面表达具有相反的作用。讨论了这些发现对IL-10介导的免疫抑制的意义。
