LACK OF INDUCTION OF SUPPRESSOR T-CELLS BY INTESTINAL EPITHELIAL-CELLS FROM PATIENTS WITH INFLAMMATORY BOWEL-DISEASE
LACK OF INDUCTION OF SUPPRESSOR T-CELLS BY INTESTINAL EPITHELIAL-CELLS FROM PATIENTS WITH INFLAMMATORY BOWEL-DISEASE
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DOI：
10.1172/jci114832
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发表时间：
1990-10-01
影响因子：
15.9
通讯作者：
EISENHARDT, D
中科院分区：
文献类型：
--
作者：
MAYER, L;EISENHARDT, D
炎症性肠病(IBD)所见的慢性持续炎症反应的机制尚不清楚。我们最近提出了正常肠道细胞的一种新的作用，即抗原提呈细胞。然而，与传统的抗原提呈细胞不同，正常的肠细胞似乎选择性地激活CD8+抗原非特异性抑制T细胞。为了确定炎症性肠病是否可能发生这一过程的失败，从正常人、克隆病、S病、溃疡性结肠炎和炎症性(憩室炎、缺血性结肠炎和金诱导性结肠炎)患者的小肠和大肠新鲜分离的肠细胞与同种异体T细胞以改良的混合淋巴细胞反应进行共培养。与正常肠细胞相比，42/42克罗恩‘S和35/38溃疡性结肠炎来源的肠上皮细胞刺激CD_4~+T细胞，而65/66和9/9的正常和炎症对照肠上皮细胞分别刺激CD_8~+T细胞(如上所述)，这表明所看到的结果不仅仅是潜在炎症的反映。此外，来自组织学受累组织和非受累组织的IBD肠细胞在选择性激活CD4+T细胞方面相似，这表明IBD上皮细胞存在更全面的缺陷。最后，来自IBD上皮细胞刺激的混合淋巴细胞培养的激活的T细胞以抗原非特异性的方式显示出强大的T辅助活性。综上所述，这些数据表明IBD患者的上皮细胞可能存在固有缺陷，导致在抗原过载的环境中无法正常刺激抑制性T细胞。
The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occuring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn''s disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn''s and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment.