Radeke H H, Schwinzer B, Resch K
Institute of Molecular Pharmacology, Medical School, Hannover, Germany.
Clin Exp Immunol. 1992 Dec;90(3):483-90. doi: 10.1111/j.1365-2249.1992.tb05871.x.
The concept of an active role of T lymphocytes in the initiation and development of autoimmune glomerulonephritis has gradually evolved from recent investigations. In the present study we started in a murine coculture system to directly examine cellular interactions of intrinsic glomerular mesangial cells (MC) and syngeneic T lymphocytes. Lymph node lymphocytes and, moreover, cloned T helper cells specifically affected syngeneic proliferating MC, causing growth inhibition and prostaglandin E2 (PGE2) release. The T cell specificity of mesangial cell responses was confirmed by demonstrating (i) that MC cocultured with other cell types showed no reaction and (ii) that additional activation of T lymphocytes by IL-2 or concanavalin A significantly enhanced the MC responses. Subsequently, we confirmed the presence of T cell factors in the supernatants responsible for the observed effects: interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF). Experiments with combinations of recombinant mouse IFN-gamma and human lymphotoxin or TNF-alpha showed that these lymphokines could substitute for the direct T lymphocyte effects causing a synergistic growth inhibition and PGE2 release from mouse MC. The observed lymphokine activities were not due to mesangiolysis as shown by neutral red uptake of MC. Pointing to the essential role of T helper cell-specific products, IFN-gamma antibodies abolished both the IFN-gamma and the combined IFN-gamma/TNF-alpha effect. Thus, our investigations with syngeneic MC-lymphocyte cocultures demonstrated that cultured MC specifically responded to T lymphocytes and their products.
T淋巴细胞在自身免疫性肾小球肾炎的起始和发展中起积极作用这一概念是从最近的研究中逐渐演变而来的。在本研究中，我们采用小鼠共培养系统直接检测内源性肾小球系膜细胞（MC）与同基因T淋巴细胞之间的细胞相互作用。淋巴结淋巴细胞，尤其是克隆的T辅助细胞，特异性地影响同基因增殖的MC，导致生长抑制和前列腺素E2（PGE2）释放。系膜细胞反应的T细胞特异性通过以下两点得到证实：（i）与其他细胞类型共培养的MC无反应；（ii）IL-2或伴刀豆球蛋白A对T淋巴细胞的额外激活显著增强了MC反应。随后，我们证实了负责观察到的效应的上清液中存在T细胞因子：干扰素-γ（IFN-γ）和肿瘤坏死因子（TNF）。重组小鼠IFN-γ与人类淋巴毒素或TNF-α组合的实验表明，这些淋巴因子可以替代直接的T淋巴细胞效应，导致小鼠MC协同生长抑制和PGE2释放。如MC的中性红摄取所示，观察到的淋巴因子活性并非由于系膜溶解。IFN-γ抗体消除了IFN-γ以及IFN-γ/TNF-α联合效应，这表明T辅助细胞特异性产物起关键作用。因此，我们对同基因MC-淋巴细胞共培养的研究表明，培养的MC对T淋巴细胞及其产物有特异性反应。
