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首页> 外文期刊>Infection and immunity >Modulation of expression of delayed hypersensitivity by mycobacterial antigen 85 fibronectin-binding proteins.
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Modulation of expression of delayed hypersensitivity by mycobacterial antigen 85 fibronectin-binding proteins.

机译:分枝杆菌抗原85纤连蛋白结合蛋白对迟发型超敏反应表达的调节。

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Although demonstration of delayed hypersensitivity to purified protein derivative of tuberculin (PPD) is an important element in the diagnosis of infection with Mycobacterium tuberculosis, many patients with tuberculosis are anergic. Several possible mechanisms for this specific lack of response have been described. We have now uncovered an additional one. T-cell fibronectin (FN), a lymphokine secreted by activated T cells, is closely associated with the initiation of delayed hypersensitivity reactions. Mycobacterial antigen 85 (Ag85) proteins have been shown to bind to plasma FN. The ability of Ag85 to bind to T-cell FN and modulate expression of delayed hypersensitivity was therefore studied. Purified Ag85 proteins from M. tuberculosis, Mycobacterium bovis BCG, or Mycobacterium kansasii bound to T-cell FN, fibroblast FN, and plasma FN in vitro. Purified 65-kDa heat shock protein (hsp65) from M. bovis BCG did not bind to any FN. Ag85, but not hsp65, inhibited the ability of T-cell FN to agglutinate monocytes in vitro in a dose-dependent manner. In vivo, mixtures of PPD or dinitrophenyl-ovalbumin and purified M. tuberculosis or M. bovis BCG Ag85 proteins elicited significantly smaller delayed hypersensitivity inflammatory reactions in sensitized guinea pigs than did PPD or dinitrophenyl-ovalbumin alone. Purified hsp65 did not inhibit expression of delayed hypersensitivity to PPD or dinitrophenyl-ovalbumin. We suggest that Ag85 proteins could inhibit in vivo expression of delayed hypersensitivity during mycobacterial infections because of their interaction with T-cell FN.
机译:尽管证明对结核菌素(PPD)纯化蛋白衍生物的迟发型超敏反应是诊断结核分枝杆菌感染的重要因素,但许多结核病患者仍是无反应的。已经描述了针对这种特定的缺乏响应的几种可能的机制。现在,我们发现了另外一个。 T细胞纤连蛋白(FN)是活化T细胞分泌的淋巴因子,与迟发型超敏反应的启动密切相关。分枝杆菌抗原85(Ag85)蛋白已显示与血浆FN结合。因此研究了Ag85与T细胞FN结合并调节迟发型超敏反应表达的能力。来自结核分枝杆菌,牛分枝杆菌BCG或堪萨斯分枝杆菌的纯化Ag85蛋白在体外与T细胞FN,成纤维细胞FN和血浆FN结合。来自牛分枝杆菌BCG的纯化的65kDa热激蛋白(hsp65)不结合任何FN。 Ag85,而不是hsp65,在体外以剂量依赖的方式抑制T细胞FN凝集单核细胞的能力。在体内,PPD或二硝基苯基-卵清蛋白与纯化的结核分枝杆菌或牛分枝杆菌BCG Ag85蛋白的混合物与单独的PPD或二硝基苯基-卵清蛋白相比,在致敏的豚鼠中引起的迟发型超敏反应性炎症反应小得多。纯化的hsp65不会抑制对PPD或二硝基苯基-卵清蛋白的迟发型超敏反应的表达。我们建议,由于Ag85蛋白与T细胞FN相互作用,因此可以抑制分枝杆菌感染期间迟发型超敏反应的体内表达。

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