Regulation of the proinflammatory effects of Fas ligand (CD95L)
Regulation of the proinflammatory effects of Fas ligand (CD95L)
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DOI：
10.1126/science.282.5394.1714
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发表时间：
1998-11-27
期刊：
影响因子：
56.9
通讯作者：
Nabel, GJ
中科院分区：
文献类型：
--
作者：
Chen, JJ;Sun, YN;Nabel, GJ
Fas配体（CD 95 L）抑制免疫豁免器官如眼和睾丸中的T细胞功能，但在大多数组织中，CD 95 L表达诱导强有力的炎症反应。用稳定转染的结肠癌细胞系CT 26-CD 95 L，确定了这些不同应答的分子基础。当皮下注射时，CT 26-CD 95 L的排斥反应是由CD 95 L激活的中性粒细胞引起的。CT 26-CD 95 L在眼内空间中存活，因为存在抑制中性粒细胞活化的转化生长因子-β（TGF-β）。向皮下部位提供TGF-β，保护其免受肿瘤排斥。因此，这些细胞因子共同产生促进免疫耐受的微环境，这可能有助于改善同种异体移植排斥反应。
Fas ligand (CD95L) inhibits T cell function in immune-privileged organs such as the eye and testis, yet in most tissues CD95L expression induces potent inflammatory responses. With a stably transfected colon carcinoma cell Line, CT26-CD95L, the molecular basis for these divergent responses was defined. When injected subcutaneously, rejection of CT26-CD95L was caused by neutrophils activated by CD95L. CT26-CD95L survived in the intraocular space because of the presence of transforming growth factor-beta (TGF-beta), which inhibited neutrophil activation. Providing TGF-beta to subcutaneous sites protected against tumor rejection. Thus, these cytokines together generate a microenvironment that promotes immunologic tolerance, which may aid in the amelioration of allograft rejection.