Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses.
Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses.
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DOI：
10.1084/jem.189.8.1169
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发表时间：
1999-04-19
期刊：
影响因子：
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通讯作者：
McGhee JR
中科院分区：
文献类型：
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作者：
Dohi T;Fujihashi K;Rennert PD;Iwatani K;Kiyono H;McGhee JR
为了研究辅助性T细胞（Th）2型应答在肠道炎症小鼠模型中的潜在作用，我们使用三硝基苯磺酸（TNBS）-半抗原在干扰素（IFN）-γ合成减少或不发生的Th1型应答情况下诱导炎症性肠病。向正常（IFN -γ +/+）或Th1缺陷的IFN -γ基因敲除（IFN -γ -/-）BALB/c小鼠结肠内给予TNBS会导致明显的结肠炎。在IFN -γ -/-小鼠中，隐窝炎症比IFN -γ +/+小鼠更严重，并且伴有结肠集合淋巴结肥大，其淋巴上皮含有M细胞以及类似派氏集合淋巴结的明显的B细胞和T细胞区。来自两组小鼠的半抗原特异性结肠集合淋巴结T细胞都表现出具有白细胞介素（IL）-4和IL -5产生的Th2表型。用抗IL -4抗体处理的正常小鼠或IL -4 -/-小鼠中的TNBS结肠炎比IFN -γ +/+或IFN -γ -/-小鼠中的病情要轻。我们的研究结果现在表明，TNBS结肠炎中的Th2型应答与结肠集合淋巴结增大和黏膜层炎症有关，并且可能代表溃疡性结肠炎的一种模型。
To investigate the potential involvement of T helper (Th)2-type responses in murine models of intestinal inflammation, we used trinitrobenzene sulfonic acid (TNBS)–hapten to induce inflammatory bowel disease in situations where Th1-type responses with interferon (IFN)-γ synthesis are either diminished or do not occur. Intracolonic administration of TNBS to either normal (IFN-γ+/+) or Th1-deficient IFN-γ knockout (IFN-γ−/−) BALB/c mice resulted in significant colitis. In IFN-γ−/− mice, crypt inflammation was more severe than in IFN-γ+/+ mice and was accompanied by hypertrophy of colonic patches with a lymphoepithelium containing M cells and distinct B and T cell zones resembling Peyer's patches. Hapten-specific, colonic patch T cells from both mouse groups exhibited a Th2 phenotype with interleukin (IL)-4 and IL-5 production. TNBS colitis in normal mice treated with anti–IL-4 antibodies or in IL-4−/− mice was less severe than in either IFN-γ+/+ or IFN-γ−/− mice. Our findings now show that the Th2-type responses in TNBS colitis are associated with colonic patch enlargement and inflammation of the mucosal layer and may represent a model for ulcerative colitis.