Itoh T, Wakatsuki Y, Yoshida M, Usui T, Matsunaga Y, Kaneko S, Chiba T, Kita T
Department of Clinical Bio-regulatory Science, Kyoto University Graduate School of Medicine, Japan.
J Gastroenterol. 1999 Oct;34(5):560-70. doi: 10.1007/s005350050373.
Helicobacter pylori infection is associated with chronic infiltration by various cell types, including T cells, whose cytokine production may regulate the inflammatory reaction as well as local immune response to the bacterium. We prospectively analyzed the constituents of the cellular infiltrates and the cytokines produced by T cells in antral biopsies obtained from 73 subjects with and without H. pylori infection, before and after eradication therapy, and compared them with a histological grade of gastritis. We found that T cells predominated in cell number, followed by granulocytes/monocytes and plasma cells in both H. pylori-infected and H. pylori-uninfected subjects. Despite the absence of H. pylori infection, more than 70% of gastric CD4-positive T cells obtained from uninfected tissue produced interferon-gamma (IFN-gamma) in the cytosol. Upon receptor cross-linking of a CD3 and a CD28 molecule, T cells in both infected and uninfected tissue continuously secreted a far greater amount of IFN-gamma than those in peripheral blood mononuclear cell controls for a period of cell culture, whereas the increase in interleukin-4 (IL-4) was very small, and no increase in IL-2 secretion was seen. In H. pylori-infected patients, IFN-gamma secretion was correlated with the grade of mononuclear cell infiltration and decreased to an uninfected control level after eradication therapy. We did not see the effect of eradication on IL-4 secretion. Anti-H. pylori antibody of the IgG2 subclass was remarkably increased in H. pylori-infected subjects. These results together suggest that gastric T cells are already differentiated to produce a large amount of IFN-gamma by a mechanism unrelated to H. pylori infection. H. pylori infection appeared to activate T cells to secrete even more IFN-gamma, which may contribute to maintaining a perpetual inflammation in H. pylori-infected stomach.
幽门螺杆菌感染与多种细胞类型的慢性浸润有关，这些细胞类型包括T细胞，其细胞因子的产生可能调节炎症反应以及对该细菌的局部免疫反应。我们前瞻性地分析了73名有或无幽门螺杆菌感染的受试者在根除治疗前后取自胃窦活检组织中的细胞浸润成分以及T细胞产生的细胞因子，并将它们与胃炎的组织学分级进行比较。我们发现，在幽门螺杆菌感染和未感染的受试者中，T细胞在数量上占主导地位，其次是粒细胞/单核细胞和浆细胞。尽管没有幽门螺杆菌感染，但从未感染组织中获取的胃CD4阳性T细胞中有超过70%在细胞质中产生γ干扰素（IFN-γ）。在CD3和CD28分子的受体交联后，在细胞培养的一段时间内，感染和未感染组织中的T细胞持续分泌的IFN-γ量远高于外周血单个核细胞对照，而白细胞介素-4（IL-4）的增加非常小，且未观察到IL-2分泌增加。在幽门螺杆菌感染的患者中，IFN-γ分泌与单核细胞浸润程度相关，根除治疗后降至未感染对照水平。我们未观察到根除对IL-4分泌的影响。在幽门螺杆菌感染的受试者中，IgG2亚类的抗幽门螺杆菌抗体显著增加。这些结果共同表明，胃T细胞已经通过与幽门螺杆菌感染无关的机制分化为产生大量IFN-γ。幽门螺杆菌感染似乎激活T细胞分泌更多的IFN-γ，这可能有助于维持幽门螺杆菌感染的胃中的持续炎症。
