Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR ζ-chain (CD3ζ)
Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR ζ-chain (CD3ζ)
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DOI：
10.4049/jimmunol.173.1.586
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发表时间：
2004-07-01
影响因子：
4.4
通讯作者：
Ochoa, AC
中科院分区：
文献类型：
--
作者：
Zabaleta, J;McGee, DJ;Ochoa, AC
幽门螺杆菌感染了大约一半的人口。感染的结果从胃炎到胃癌不等，似乎与对H. pylori..发生非萎缩性胃炎的患者呈现Th 1应答而不产生保护性免疫，这表明该细菌可能具有逃避宿主免疫应答的机制。几个H.幽门螺杆菌蛋白质可通过尚不清楚的机制在体外损害巨噬细胞和T细胞功能。我们测试了H. pylori提取物和活H. pylori对Jurkat细胞和新鲜分离的人正常T淋巴细胞的作用，以确定细菌可能损害T细胞功能的可能机制。Jurkat细胞或活化的T淋巴细胞与H. pylori超声处理物具有降低的增殖，这不是由T细胞凋亡或早期T细胞信号传导事件中的损伤引起的。相反，H. pylori超声灭活活H. pylori诱导TCR的CD 3 ζ-链的表达降低。共培养活H. pylori与T细胞的实验表明，野生型菌株，而不是pylori酶突变体rocF（-），耗尽L-精氨酸，并导致CD 3 zeta表达下降。此外，酶抑制剂逆转了这些事件。这些结果表明，H.幽门螺杆菌尿素酶不仅对尿素的产生很重要，而且在感染过程中也可能损害T细胞功能。
Helicobacter pylori infects approximately half the human population. The outcomes of the infection range from gastritis to gastric cancer and appear to be associated with the immunity to H. pylori.. Patients developing nonatrophic gastritis present a Th1 response without developing protective immunity, suggesting that this bacterium may have mechanisms to evade the immune response of the host. Several H. pylori proteins can impair macrophage and T cell function in vitro through mechanisms that are poorly understood. We tested the effect of H. pylori extracts and live H. pylori on Jurkat cells and freshly isolated human normal T lymphocytes to identify possible mechanisms by which the bacteria might impair T cell function. Jurkat cells or activated T lymphocytes cultured with an H. pylori sonicate had a reduced proliferation that was not caused by T cell apoptosis or impairment in the early T cell signaling events. Instead, both the H. pylori sonicate and live H. pylori induced a decreased expression of the CD3zeta-chain of the TCR. Coculture of live H. pylori with T cells demonstrated that the wild-type strain, but not the arginase mutant rocF(-), depleted L-arginine and caused a decrease in CD3zeta expression. Furthermore, arginase inhibitors reversed these events. These results suggest that H. pylori arginase is not only important for urea production, but may also impair T cell function during infection.