CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice
CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice
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DOI：
10.4049/jimmunol.166.11.6972
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发表时间：
2001-06-01
影响因子：
4.4
通讯作者：
Powrie, F
中科院分区：
文献类型：
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作者：
Malmström, V;Shipton, D;Powrie, F
在缺乏调节性T细胞的情况下，将CD 45 RB（高）CD 4（+）T细胞转移至免疫缺陷小鼠导致Th 1介导的结肠炎。在这项研究中，我们发现肠道炎症的特征是与BALB/c小鼠相比，肠系膜淋巴结（MLN）中CD 134 L（+）（OX 40 L（+））激活的DC数量增加了15倍。这在功能上是重要的，因为给予抗CD 134 L mAb抑制MLN中T细胞的增殖及其肠道归巢整合素α（4）β（7）的表达。最重要的是，抗CD 134 L mAb完全阻断了结肠炎的发展。令人惊讶的是，发现CD 134 L在未重构的SCID小鼠的MLN中由一定比例的树突状细胞（DC）表达，这表明在不存在T细胞来源的信号的情况下，可以在DC上诱导CD 134 L。这些结果表明，在SCID小鼠的MLN中的一些DC表达活化的表型，并且这些细胞的CD 134 L表达参与由T细胞转移诱导的结肠炎的发展。调节性T细胞的共转移抑制了CD 134 L（+）DC的积累，这表明抑制活化DC的积累是这些细胞预防免疫病理学的一种机制。
Transfer of CD45RB(high) CD4(+) T cells to immune-deficient mice in the absence of regulatory T cells leads to a Th1-mediated colitis. In this study, we show that intestinal inflammation is characterized by a 15-fold increase in the number of CD134L(+) (OX40L(+))-activated DC in the mesenteric lymph nodes (MLNs) compared with BALB/c mice. This was important functionally, as administration of an anti-CD134L mAb inhibited the proliferation of T cells in the MLNs as well as their expression of the gut-homing integrin alpha (4)beta (7). Most importantly, the anti-CD134L mAb completely blocked development of colitis. Surprisingly, CD134L was found to be expressed by a proportion of dendritic cells (DC) in the MLNs of unreconstituted SCID mice, suggesting that CD134L can be induced on DC in the absence of T cell-derived signals. These results indicate that some DC in the MLNs of SCID mice express an activated phenotype and that CD134L expression by these cells is involved in the development of colitis induced by T cell transfer. Accumulation of CD134L(+) DC was inhibited by cotransfer of regulatory T cells, suggesting that inhibition of the accumulation of activated DC is one mechanism by which these cells prevent immune pathology.