Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction
Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction
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DOI：
10.4049/jimmunol.167.11.6330
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发表时间：
2001-12-01
影响因子：
4.4
通讯作者：
Ware, CF
中科院分区：
文献类型：
--
作者：
Shaikh, RB;Santee, S;Ware, CF
LIGHT是细胞因子TNF家族的一员（与光敏素同源，表现出可诱导的表达，并与HSV糖蛋白D竞争疱疹病毒进入介体，一种在T细胞上表达的受体），在活化的T细胞上被诱导，并介导体外共刺激和抗肿瘤活性。关于LIGHT表达的体内效应的信息相对较少，特别是在T细胞区室内。在这项工作中，我们描述了在CD2启动子的控制下表达人LIGHT的转基因小鼠，导致T淋巴细胞谱系细胞中的组成型转基因表达。LIGHT转基因动物表现出淋巴组织结构和淋巴细胞亚群分布的异常。它们还表现出炎症的迹象，其中肠道最严重，沿着生殖器官的组织破坏。当免疫缺陷小鼠用来自LIGHT转基因供体小鼠的骨髓重建时，这些LIGHT介导的作用被重现。LIGHT转基因小鼠中的T细胞具有活化的表型，并且粘膜T细胞表现出增强的Th1细胞因子活性。结果表明，LIGHT可能作为T细胞活化的重要调节剂发挥作用，并涉及粘膜组织炎症中的LIGHT信号通路。
LIGHT, a member of the TNF family of cytokines (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for herpesvirus entry mediator, a receptor expressed on T cells), is induced on activated T cells and mediates costimulatory and antitumor activity in vitro. Relatively little information is available on the in vivo effects of LIGHT expression, particularly within the T cell compartment. In this work, we describe transgenic mice that express human LIGHT under the control of the CD2 promoter, resulting in constitutive transgene expression in cells of the T lymphocyte lineage. LIGHT-transgenic animals exhibit abnormalities in both lymphoid tissue architecture and the distribution of lymphocyte subsets. They also show signs of inflammation that are most severe in the intestine, along with tissue destruction of the reproductive organs. These LIGHT-mediated effects were recapitulated when immune-deficient mice were reconstituted with bone marrow from LIGHT-transgenic donor mice. T cells in the LIGHT-transgenic mice have an activated phenotype and mucosal T cells exhibit enhanced Th1 cytokine activity. The results indicate that LIGHT may function as an important regulator of T cell activation, and implicate LIGHT signaling pathways in inflammation focused on mucosal tissues.