Banu N, Meyers C M
University of Pennsylvania School of Medicine, Penn Center for the Molecular Studies of Kidney Diseases, Department of Medicine, Philadelphia 19104, USA.
Kidney Int. 1999 Sep;56(3):985-94. doi: 10.1046/j.1523-1755.1999.00645.x.
We examined the immunomodulatory effects of transforming growth factor-beta1 (TGF-beta1) on the regulation of class II MHC and costimulatory molecule expression in a primary renal tubular epithelial cell line, called F1K.
Class II major histocompatibility complex (MHC), class II transactivator, B7-1, intercellular adhesion molecule-1 (ICAM-1) and interferon-gamma (IFN-gamma) receptor beta chain were evaluated in untreated and cytokine-treated F1K by Northern hybridization analysis and flow cytometry. T cell activation studies were performed to assess TGF-beta1-mediated effects on antigen presenting cell function of F1K.
Pretreatment of F1K with TGF-beta1 markedly inhibited IFN-gamma-induced class II MHC expression, by both FACS and Northern analysis. Total class II transactivator mRNA levels were also diminished by TGF-beta1, indicating that class II MHC modulation in F1K results from inhibition of this intermediate protein. As previous studies demonstrated that cotreatment of F1K cells with IFN-gamma + lipopolysaccharide (LPS) induces B7-1, we evaluated the potential regulatory effects of TGF-beta1 exposure on B7-1 expression. Our studies revealed that B7-1 mRNA and cell-surface expression in IFN-gamma + LPS-treated F1K were decreased by TGF-beta1 pretreatment. Functional studies evaluating TGF-beta1-mediated effects were performed with IFN-gamma + LPS-treated F1K and MR1.3, a nephritogenic CD4+ Th2 clone derived from kidneys of animals with autoimmune glomerulonephritis. Interleukin (IL)-4 production assays demonstrated activation of MR1. 3 by IFN-gamma + LPS-treated cells, but not by IFN-gamma + LPS-treated cells previously exposed to TGF-beta1, indicating that TGF-beta1-mediated inhibition of class II MHC and B7-1 expression alters the antigen presenting cell function of F1K.
These studies describe the proscriptive influence of TGF-beta1 on class II MHC and B7-1 expression in renal tubular epithelial cells. Such findings indicate that TGF-beta1 alters the antigen presenting cell function of renal tubular epithelial cells in vitro, and suggest a potential mechanism for immunosuppression of T cell-mediated renal immune responses in vivo.
我们研究了转化生长因子-β1（TGF-β1）对一种原代肾小管上皮细胞系F1K中II类主要组织相容性复合体（MHC）和共刺激分子表达调控的免疫调节作用。
通过Northern杂交分析和流式细胞术，对未处理及细胞因子处理的F1K细胞中的II类主要组织相容性复合体（MHC）、II类反式激活因子、B7-1、细胞间黏附分子-1（ICAM-1）和干扰素-γ（IFN-γ）受体β链进行评估。进行T细胞活化研究以评估TGF-β1对F1K抗原呈递细胞功能的介导作用。
通过流式细胞术和Northern分析，用TGF-β1预处理F1K可显著抑制IFN-γ诱导的II类MHC表达。TGF-β1还降低了II类反式激活因子的总mRNA水平，表明F1K中II类MHC的调节是由于该中间蛋白的抑制。由于先前的研究表明F1K细胞与IFN-γ+脂多糖（LPS）共同处理可诱导B7-1表达，我们评估了TGF-β1暴露对B7-1表达的潜在调节作用。我们的研究表明，TGF-β1预处理可降低IFN-γ+LPS处理的F1K细胞中B7-1的mRNA和细胞表面表达。使用IFN-γ+LPS处理的F1K细胞和MR1.3（一种源自自身免疫性肾小球肾炎动物肾脏的致肾炎性CD4+Th2克隆）进行了评估TGF-β1介导作用的功能研究。白细胞介素（IL）-4产生试验表明，IFN-γ+LPS处理的细胞可激活MR1.3，但先前暴露于TGF-β1的IFN-γ+LPS处理的细胞则不能激活，这表明TGF-β1介导的II类MHC和B7-1表达抑制改变了F1K的抗原呈递细胞功能。
这些研究描述了TGF-β1对肾小管上皮细胞中II类MHC和B7-1表达的抑制性影响。这些发现表明，TGF-β1在体外改变了肾小管上皮细胞的抗原呈递细胞功能，并提示了体内T细胞介导的肾脏免疫反应免疫抑制的潜在机制。
