Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin
Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin
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DOI：
10.1128/iai.01063-06
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Cover, Timothy L.
中科院分区：
文献类型：
--
作者：
Algood, Holly M. Scott;Torres, Victor J.;Cover, Timothy L.
幽门螺杆菌在人体胃中的持续定植是胃癌和消化性溃疡疾病发展的危险因素。H.幽门螺杆菌分泌一种毒素，VacA，靶向人类胃上皮细胞和T淋巴细胞，并增强H. pylori在小鼠模型中定殖于胃。研究VacA对H. pylori在小鼠胃中的定植，我们研究了海洋T淋巴细胞是否对VacA活性敏感。VacA抑制鼠T细胞系（LBRM-33）产生白细胞介素-2（IL-2），与其对人T细胞系（Jurkat）的作用相似，但不抑制原代鼠脾细胞或CD 4（+）T细胞产生IL-2。VacA抑制活化诱导的原代人CD 4（+）T细胞增殖，但不抑制原代鼠CD 4（+）T细胞增殖。流式细胞术研究表明，与原代鼠CD 4（+）T细胞结合的VacA水平显著低于与人CD 4（+）T细胞结合的VacA水平。这表明，原代鼠CD 4（+）T细胞对VacA的抗性至少部分归因于VacA与这些细胞的结合受损。
Persistent colonization of the human stomach by Helicobacter pylori is a risk factor for the development of gastric cancer and peptic ulcer disease. H. pylori secretes a toxin, VacA, that targets human gastric epithelial cells and T lymphocytes and enhances the ability of H. pylori to colonize the stomach in a mouse model. To examine how VacA contributes to H. pylori colonization of the mouse stomach, we investigated whether marine T lymphocytes were susceptible to VacA activity. VacA inhibited interleukin-2 (IL-2) production by a murine T-cell line (LBRM-33), similar to its effects on a human T-cell line (Jurkat), but did not inhibit IL-2 production by primary murine splenocytes or CD4(+) T cells. VacA inhibited activation-induced proliferation of primary human CD4(+) T cells but did not inhibit the proliferation of primary murine CD4(+) T cells. Flow cytometry studies indicated that the levels of VacA binding to primary murine CD4(+) T cells were significantly lower than levels of VacA binding to human CD4(+) T cells. This suggests that the resistance of primary murine CD4(+) T cells to VacA is attributable, at least in part, to impaired VacA binding to these cells.