Roles of CD8^+T lymphocyte in intestinal nematode infection

CD8^T淋巴细胞在肠道线虫感染中的作用

基本信息

批准号：
11670248
负责人：
MATSUDA Shinji
金额：
$ 1.15万
依托单位：
AKITA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670248/
关键词：
nematode mesenteric lymph node cytokines CD4^+T lymphocytes CD8^+T lymphocytes rats mouse pathology Nippostrongylus brasiliensis 腸管寄生線虫 mRNA

项目摘要

Both CD4^+ and CD8^+T lymphocytes in the mesenteric lymph node (MLN) proliferated markedly 2 weeks after infection with Nippostrongylus brasiliensis (Nb) in rats or 7 to 10 days after infection in mice, when MLN swelling reached the maximum. After infection, CD4^+ showed high levels of IL-3, IL-4, IL-5, and IL-13 gene expression, which was scarcely detected before infection. In CD8^+, IL-3, IL-5, and IL-13 mRNAs increased greatly, but IL-4 mRNA was not detected at all after infection. IL-10 mRNA was strongly enhanced in CD8^+ after infection, while detected at high levels before and after infection in CD4^+. An ELISPOT assay also showed that there were few if any CD8^+T cells which actually produced IL-4 in murine MLN after infection, while many CD4^+T cells produced this cytokine. The excretory-secretory antigens (ES) obtained from adult worms suppressed the productivity of IFN-γ in both CD4^+ and CD8^+T cells in a dose-dependent manner. This seemed to be a direct effect of ES to lymp … More hocytes without involving the activation in type2 cytokines, because it did not affect IL-4 production from CD4^+ and that of IL-10 from both CD4^+ and CD8^+. The results that only IL-4 mRNA in type2 cytokines was not detected in CD8^+ after infection despite of suppression in IFN-γ production may suggest that there are some mechanisms in which IL-4 gene expression is specifically inhibited in CD8^+. To investigate the roles of CD8^+T cells, histological changes in the intestine and changes in levels of cytokine gene expression in the MLN were compared between normal mice and anti-CD8 antibody-injected mice or CD8-deficient mice after Nb infection. The pathological changes peaked at day 7 after infection, which showed mild inflammation in propria mucosa and submucosa, and the severity of histological changes and the repairing process were similar in both groups. The gene expression in cytokines such as IL-4, Il-10, IL-13, and IFN-γ did not show significant differences between them. Taken together, it has been revealed that both CD4^+ and CD8^+T cells greatly increase in MLN after Nb infection, but the pattern of cytokine gene expression in CD8^+ is different from that in CD4^+. It was suggested, however, that CD8^+T cells were not largely involved in the development of histological changes and repairing process or in the induction of cytokine milieu in the nematode infection. Less

大鼠感染巴西圆线虫（Nb）后2周或小鼠感染后7至10天，肠系膜淋巴结（MLN）中的CD4^+和CD8^+T淋巴细胞均显着增殖，此时MLN肿胀达到最大。感染后，CD4^+表现出高水平的IL-3、IL-4、IL-5和IL-13基因表达，这在感染前几乎检测不到。感染后CD8^+、IL-3、IL-5和IL-13 mRNA大幅增加，但完全检测不到IL-4 mRNA；感染后CD8^+中IL-10 mRNA增强，而感染后CD8^+中检测到IL-10 mRNA。 ELISPOT 还显示，感染后小鼠 MLN 中几乎没有检测到真正产生 IL-4 的 CD8^+ T 细胞，而许多 CD4^+ T 细胞产生这种细胞因子。这成虫的排泄分泌抗原 (ES) 以剂量依赖性方式抑制 CD4^+ 和 CD8^+T 细胞中 IFN-γ 的生产力，这似乎是 ES 对获得的淋巴细胞的直接影响。获得的 h 细胞没有 2 型细胞因子的激活，因为它不影响 CD4^+ 产生的 IL-4 以及 CD4^+ 和 CD8^+ 产生的 IL-10。结果表明 2 型中只有 IL-4 mRNA。尽管 IFN-γ 产生受到抑制，但感染后 CD8^+ 中未检测到细胞因子，这可能表明存在一些机制，其中 IL-4 基因表达在 CD8^+ 中被特异性抑制。为了研究 CD8^+ T 细胞的作用。比较Nb感染后正常小鼠和注射抗CD8抗体的小鼠或CD8缺陷小鼠的肠道组织学变化和MLN中细胞因子基因表达水平的变化，病理变化在第7天达到峰值。感染后，两组粘膜固有层和粘膜下层均表现出轻度炎症，且组织学改变的严重程度和修复过程相似，IL-4、IL-10、IL-13、IFN-γ等细胞因子的基因表达量也相似。综合来看，Nb感染后MLN中CD4^+和CD8^+T细胞均大幅增加，但CD8^+中细胞因子基因表达模式为然而，与CD4^+不同的是，CD8^+T细胞并不主要参与线虫感染中的组织学变化和修复过程或细胞因子环境的诱导。