Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4.
Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4.
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DOI：
10.1084/jem.20030097
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发表时间：
2003-07-07
期刊：
影响因子：
--
通讯作者：
Streilein JW
中科院分区：
文献类型：
--
作者：
Sugita S;Streilein JW
单层色素上皮 (PE) 排列在虹膜 PE (IPE)、睫状体 PE 和内眼的视网膜 PE（免疫豁免部位）上。这些神经嵴衍生的上皮细胞通过不明确的分子机制参与眼部免疫特权。从不同眼组织培养的小鼠 PE 细胞通过不同的机制抑制 T 细胞活化。特别是，IPE 细胞主要通过直接细胞间接触进行抑制。通过检查众多候选分子（肿瘤坏死因子受体 [TNFR]1、TNFR2、CD36、CD40、CD47、CD80、CD86、PD-L1、CD95 配体和 I 型干扰素受体）的表面表达，我们报告 IPE 细胞在其表面独特地表达共刺激分子 CD86。当用抗 CD86 阻断 IPE 或源自 CD80/CD86（但不是 CD80）敲除 (KO) 小鼠时，细胞表现出抑制 T 细胞活化的能力降低。在存在细胞毒性 T 淋巴细胞相关抗原 4 (CTLA-4) 免疫球蛋白的情况下，或者如果 T 细胞是从 CTLA-4（但不是 CD28）KO 小鼠中获得的，IPE 也无法抑制 T 细胞的激活。我们得出结论，虹膜色素上皮细胞组成性表达细胞表面CD86，这使得细胞能够通过与CTLA-4的直接相互作用来接触抑制性T细胞。因此，眼部免疫特权部分是通过颠覆通常用于传统免疫共刺激的分子来实现的。
A monolayer of pigment epithelium (PE) lines the iris PE (IPE), ciliary body PE, and retina PE of the inner eye, an immune-privileged site. These neural crest-derived epithelial cells participate in ocular immune privilege through poorly defined molecular mechanisms. Murine PE cells cultured from different ocular tissues suppress T cell activation by differing mechanisms. In particular, IPE cells suppress primarily via direct cell to cell contact. By examining surface expression of numerous candidate molecules (tumor necrosis factor receptor [TNFR]1, TNFR2, CD36, CD40, CD47, CD80, CD86, PD-L1, CD95 ligand, and type I interferon receptor), we report that IPE cells uniquely express on their surface the costimulatory molecule CD86. When IPE were blocked with anti-CD86 or were derived from CD80/CD86 (but not CD80) knockout (KO) mice, the cells displayed reduced capacity to suppress T cell activation. IPE also failed to suppress activation of T cells in the presence of cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) immunoglobulin or if the T cells were obtained from CTLA-4 (but not CD28) KO mice. We conclude that iris pigment epithelial cells constitutively express cell surface CD86, which enables the cells to contact inhibit T cells via direct interaction with CTLA-4. Thus, ocular immune privilege is achieved in part by subversion of molecules that are usually used for conventional immune costimulation.
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DOI：
10.1084/jem.20021139
发表时间：
2002-11-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Levings MK;Sangregorio R;Sartirana C;Moschin AL;Battaglia M;Orban PC;Roncarolo MG
通讯作者：
Roncarolo MG
影响因子：
64.8
作者：
BELLGRAU, D;GOLD, D;DUKE, RC
通讯作者：
DUKE, RC
影响因子：
64.5
作者：
SUDA, T;TAKAHASHI, T;NAGATA, S
通讯作者：
NAGATA, S
影响因子：
56.9
作者：
GRIFFITH, TS;BRUNNER, T;FERGUSON, TA
通讯作者：
FERGUSON, TA
影响因子：
2
作者：
KNISELY, TL;BLEICHER, PA;GRANSTEIN, RD
通讯作者：
GRANSTEIN, RD