Cross-primed CD8+ cytotoxic T cells induce severe helicobacter-associated gastritis in the absence of CD4+ T cells
Cross-primed CD8+ cytotoxic T cells induce severe helicobacter-associated gastritis in the absence of CD4+ T cells
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DOI：
10.1111/j.1523-5378.2007.00536.x
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发表时间：
2007-10-01
期刊：
影响因子：
4.4
通讯作者：
Chiba, Tsutomu
中科院分区：
文献类型：
--
作者：
Fukui, Toshiro;Nishio, Akiyoshi;Chiba, Tsutomu
背景：虽然先前的研究报道了CD4(+) 1型辅助性T细胞和调节性T细胞在幽门螺杆菌相关性胃炎中的重要作用，但CD8（+）细胞毒性T细胞的意义尚不清楚。为了研究CD8(+) T细胞的作用，我们检测了猫幽门螺杆菌感染的主要组织相容性复合体（MHC） II类缺陷（II-/-）小鼠胃粘膜的免疫应答，这些小鼠缺乏CD4(+) T细胞。材料和方法：对野生型和MHCⅱ/-型感染小鼠的胃进行组织学和免疫组织化学检查。胃酸和血清抗h。检测猫的抗体。研究促炎和抗炎细胞因子、fas配体、穿孔素和Foxp3基因在胃黏膜中的表达。结果：感染MHC II-/-的小鼠出现了严重的胃炎，伴有CD8（+）细胞的明显浸润。在接种后1和2个月，MHC II-/-小鼠的粘膜炎症和萎缩更为严重，尽管在接种后3个月胃炎已达到类似的晚期。感染MHC II-/-小鼠胃黏膜CD4（+）细胞浸润少，未见foxp3阳性细胞。MHCⅱ-/-感染小鼠白细胞介素-1 β和fas -配体基因表达上调，Foxp3基因表达下调。血清抗h。在感染MHC II-/-的小鼠中，尽管有严重的胃炎，但felis抗体较低。结论：本研究提示交叉启动CD8（+）细胞毒性T细胞可在缺乏CD4（+）辅助性T细胞的情况下诱导严重h -相关性胃炎，foxp3阳性细胞可能在胃炎症的控制中起重要作用。
Background: Although previous studies have reported important roles of CD4(+) type1-helper T cells and regulatory T cells in Helicobacter-associated gastritis, the significance of CD8(+) cytotoxic T cells remains unknown. To study the roles of CD8(+) T cells, we examined the immune response in the gastric mucosa of Helicobacter felis-infected major histocompatibility complex (MHC) class II-deficient (II-/-) mice, which lack CD4(+) T cells.Materials and methods: Stomachs from H. felis-infected wild-type and infected MHC II-/- mice were examined histologically and immunohistochemically. Gastric acidity and serum levels of anti-H. felis antibodies were measured. The expression of pro-inflammatory and anti-inflammatory cytokine, Fas-ligand, perforin, and Foxp3 genes in the gastric mucosa was investigated.Results: H. felis-infected MHC II-/- mice developed severe gastritis, accompanied by marked infiltration of CD8(+) cells. At 1 and 2 months after inoculation, mucosal inflammation and atrophy were more severe in MHC II-/- mice, although gastritis had reached similar advanced stages at 3 months after inoculation. There was little infiltration of CD4(+) cells, and no Foxp3-positive cells were detected in the gastric mucosa of the infected MHC II-/- mice. The expression of the interleukin-1 beta and Fas-ligand genes was up regulated, but that of Foxp3 was down regulated in the infected MHC II-/- mice. Serum levels of anti-H. felis antibodies were lower in the infected MHC II-/- mice, despite severe gastritis.Conclusions: The present study suggests that cross-primed CD8(+) cytotoxic T cells can induce severe H.-associated gastritis in the absence of CD4(+) helper T cells and that Foxp3-positive cells may have an important role in the control of gastric inflammation.