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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >T cell surface redox levels determine T cell reactivity and arthritis susceptibility
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T cell surface redox levels determine T cell reactivity and arthritis susceptibility

机译：T细胞表面氧化还原水平决定T细胞反应性和关节炎易感性

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摘要

Rats and mice with a lower capacity to produce reactive oxygen species (ROS) because of allelic polymorphisms in the Ncfl gene (which encodes neutrophil cytosolic factor 1) are more susceptible to develop severe arthritis. These data suggest that ROS are involved in regulating the immune response. We now show that the lower capacity to produce ROS is associated with an increased number of reduced thiol groups (-SH) on T cell membrane surfaces. Artificially increasing the number of reduced thiols on T cells from animals with arthritis-protective Ncf1 alleles by glutathione treatment lowered the threshold for T cell reactivity and enhanced proliferative responses in vitro and in vivo. Importantly, T cells from immunized congenic rats with an E3-derived Ncfl allele (DA.Ncf1(E3) rats) that cannot transfer arthritis to rats with an arthritis-associated Dark Agouti (DA)-derived mutated Ncf1 allele (DA.Ncf1(DA) rats) became arthritogenic after increasing cell surface thiol levels. This finding was confirmed by the reverse experiment, in which oxidized T cells from DA.Ncf1(DA) rats induced less severe arthritis compared with controls. Therefore, we conclude that ROS production as controlled by Ncf1 is important in regulating surface redox levels of T cells and thereby suppresses autoreactivity and arthritis development.
机译：由于Ncfl基因（编码嗜中性粒细胞胞浆因子1）中的等位基因多态性，具有较低能力产生活性氧（ROS）的大鼠和小鼠更容易患上严重的关节炎。这些数据表明ROS参与调节免疫应答。我们现在表明，较低的生产ROS的能力与T细胞膜表面上减少的巯基（-SH）数量增加有关。通过谷胱甘肽处理，人工增加患有关节炎保护性Ncf1等位基因的动物的T细胞上还原的硫醇数量，降低了T细胞反应性的阈值，并增强了体内和体外的增殖反应。重要的是，来自具有E3衍生的Ncfl等位基因（DA.Ncf1（E3）大鼠）的免疫同基因大鼠的T细胞不能将关节炎转移至患有关节炎相关的黑暗刺痛（DA）衍生的Ncf1等位基因（DA.Ncf1（ DA）大鼠）在增加细胞表面硫醇水平后成为致关节炎的物质。这项逆向实验证实了这一发现，在逆向实验中，与对照组相比，来自DA.Ncf1（DA）大鼠的氧化T细胞诱发的严重关节炎更少。因此，我们得出结论，由Ncf1控制的ROS的产生在调节T细胞的表面氧化还原水平中很重要，从而抑制了自身反应性和关节炎的发展。

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