Retinal and ciliary body pigment epithelium suppress activation of T lymphocytes via transforming growth factor beta
Retinal and ciliary body pigment epithelium suppress activation of T lymphocytes via transforming growth factor beta
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DOI：
10.1016/j.exer.2006.08.005
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发表时间：
2006-12-01
影响因子：
3.4
通讯作者：
Mochizuki, Manabu
中科院分区：
文献类型：
--
作者：
Sugita, Sunao;Futagami, Yuri;Mochizuki, Manabu
眼部微环境具有免疫抑制和抗炎作用。从眼睛中分离出来的色素上皮 (PE) 细胞具有在体外抑制 T 细胞受体依赖性 T 细胞活化的新特性。这一特性取决于它们产生细胞表面和可溶性抑制分子的能力。虹膜色素上皮 (IPE) 通过与初始 T 细胞的直接细胞间接触来实现这一点，这种抑制性接触是由 B7 和 IPE 上组成型表达的膜结合 TGF β 之间的相互作用介导的。我们现在已经通过类似的过程检查了其他眼部 PE 细胞，例如视网膜色素上皮 (RPE) 和睫状体色素上皮 (CBPE) 是否具有类似的抑制特性。我们发现 RPE 和 CBPE 通过可溶性抑制因子显着抑制旁观 T 细胞的激活。 RPE和CBPE分泌不同的可溶性抑制因子，包括TGF beta 1和TGF beta 2。虽然IPE细胞通过膜结合的TGF beta抑制旁观者T细胞的激活，但RPE和CBPE通过独立于细胞接触的机制通过可溶形式的活性TGF来抑制旁观者T细胞的激活。这些眼部 PE 细胞能够通过增强包括 TGF beta 在内的调节性细胞因子的产生来改变 T 细胞功能。我们认为，这种通过 TGF 抑制的机制确保可溶性活性 TGF β 释放到眼部微环境中，从而创造眼后段的免疫特权。 (c) 2006 Elsevier Ltd. 保留所有权利。
The ocular microenvironment is immunosuppressive and anti-inflammatory. Pigment epithelial (PE) cells isolated from the eye possess a new property of suppressing T cell receptor-dependent activation of T cells in vitro. This property depends on their capacity to produce cell-surface and soluble inhibitory molecules. The iris pigment epithelia (IPE) do so through direct cell-to-cell contact with naive T cells, and this suppressive contact is mediated by interactions between B7 and membrane-bound TGF beta that are expressed constitutively on IPE. We have now examined whether other ocular PE cells, e.g., retinal pigment epithelia (RPE) and ciliary body pigment epithelia (CBPE), have a similar suppressive property by a similar process. We have found that RPE and CBPE significantly suppress the activation of bystander T cells via soluble inhibitory factors. RPE and CBPE secrete different soluble inhibitory factors including TGF beta 1 and TGF beta 2. Although IPE cells suppress the activation of bystander T cells by membrane-bound TGF beta, the RPE and CBPE do so by soluble forms of active TGF through mechanisms independent of cell contact. These ocular PE cells are capable modifying T cell function by enhancing production of regulatory cytokines including TGF beta. We propose that this mechanism of suppression via TGF ensures that soluble active TGF beta is released into the ocular microenvironment in order to create the immune privilege of the posterior segment of the eye. (c) 2006 Elsevier Ltd. All rights reserved.