Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease
Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease
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DOI：
10.4049/jimmunol.174.9.5814
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Mayer, L
中科院分区：
文献类型：
--
作者：
Brimnes, J;Allez, M;Mayer, L
据信粘液耐受部分由调节性T细胞介导。肠上皮细胞（IEC）可能在这种调节细胞的产生中发挥重要作用，因为它们能够加工并将Ag呈递给T细胞。此外，我们先前已经证明IEC能够在体外产生调节性CD 8（+）T细胞。在本研究中，我们分析了正常人和炎症性肠病（IBD）患者固有层（LP）淋巴细胞中是否存在这种调节性CD 8（+）T细胞。本研究的结果表明，来自正常对照的LP CD 8（+）T细胞具有调节活性，而未分级分离的LP淋巴细胞和纯化的LP CD 4（+）T细胞均不具有调节活性。LP CD 8（+）T细胞以细胞接触依赖性方式抑制美洲商陆促分裂原刺激的PBMC产生IG 31- 80%。CD 28（+）和CD 28（-）CD 8（+）LP T细胞之间的抑制没有观察到显著差异。与正常LP中的CD 8（+）T细胞相反，IBD患者LP中分离的CD 8（+）T细胞不抑制美洲商陆丝裂原刺激PBMC产生IG（6个溃疡性结肠炎标本中的5个; 6个克罗恩病标本中的6个）。此外，我们还证实，与正常LP相比，IBD LP中TCR V β 5.1阳性CD 8（+）T细胞的频率降低，我们先前已证实这些T细胞具有调节作用，并在体外被IEC扩增。总之，这项研究表明，具有调节活性的CD 8（+）T细胞存在于正常健康个体的LP中，但在IBD患者中不存在，这表明这些细胞可能在粘膜耐受中发挥积极作用。
Mucosal tolerance is believed to be partly mediated by regulatory T cells. Intestinal epithelial cells (IECs) may play an important role in the generation of such regulatory cells, because they are able to process and present Ag to T cells. Furthermore, we have previously demonstrated that IECs are able to generate regulatory CD8(+) T cells in vitro. In the present study, we have analyzed lamina propria (LP) lymphocytes for the presence of such regulatory CD8(+) T cells in normal individuals as well as in patients with inflammatory bowel disease (IBD). The results of the present study show that LP CD8(+) T cells derived from normal controls possess regulatory activity, whereas both unfractionated LP lymphocytes and purified LP CD4(+) T cells do not. The LP CD8(+) T cells suppress Ig production by pokeweed mitogen-stimulated PBMCs by 31-80%, in a cell contact-dependent manner. No significant difference in suppression between CD28(+) and CD28(-)CD8(+) LP T cells was observed. In contrast to CD8(+) T cells from normal LP, CD8(+) T cells isolated from LP of IBD patients, did not suppress Ig production by pokeweed mitogen-stimulated PBMC (five of six ulcerative colitis specimens; six of six Crohn's disease specimens). Furthermore, we demonstrate that the frequency of TCR V beta 5.1-positive CD8(+) T cells, which we previously have demonstrated to be regulatory and to be expanded by IECs in vitro, is decreased in IBD LP compared with normal LP. In conclusion, this study demonstrates that CD8(+) T cells with regulatory activity are present in the LP of normal healthy individuals, but not in patients with IBD, suggesting that these cells might play an active role in mucosal tolerance.