Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
J Immunol. 2010 Feb 1;184(3):1589-95. doi: 10.4049/jimmunol.0901582. Epub 2009 Dec 30.
CD4(+) regulatory T cell (Treg) populations are believed to play very important roles in the suppression of immune responses. Overriding Treg inhibition is necessary for initiating primary immune reaction upon inflammatory Ag stimulation. LIGHT, TNF superfamily member 14, has been shown to be a costimulatory molecule for effector T cells. Overexpression of lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) on T cells induces strong T cell-mediated experimental intestinal inflammation. How this process is initiated by LIGHT in suppressive intestinal environments remains incompletely understood. In this study, we assessed the effect of LIGHT on Tregs. Our results indicate that LIGHT can support the expansion and function of Tregs. However, when LIGHT was highly expressed, these abundant Tregs failed to suppress the development of T cell-mediated experimental colitis and antitumor immunity. We showed that this might be, in part, due to an ability of LIGHT to promote effector T cell proliferation and differentiation even in a Treg-abundant environment. Our data collectively suggest that LIGHT might be a critical cytokine involved in the development of autoimmune inflammatory diseases and that LIGHT-targeted immunotherapy might be useful in the treatment of these diseases.
CD4(+) 调节性 T 细胞（Treg）群体被认为在抑制免疫反应方面发挥着非常重要的作用。在炎症抗原刺激时，需要克服 Treg 的抑制作用，以启动初始免疫反应。LIGHT，肿瘤坏死因子超家族成员 14，已被证明是效应 T 细胞的共刺激分子。在 T 细胞上过度表达与疱疹病毒进入介体竞争结合糖蛋白 D 的淋巴毒素相关诱导配体（LIGHT）可诱导强烈的 T 细胞介导的实验性肠道炎症。LIGHT 在抑制性肠道环境中如何启动这一过程尚不完全清楚。在这项研究中，我们评估了 LIGHT 对 Treg 的影响。我们的结果表明，LIGHT 可以支持 Treg 的扩增和功能。然而，当 LIGHT 高表达时，这些丰富的 Treg 未能抑制 T 细胞介导的实验性结肠炎和抗肿瘤免疫的发展。我们表明，这可能部分是由于 LIGHT 能够促进效应 T 细胞的增殖和分化，即使在 Treg 丰富的环境中也是如此。我们的数据表明，LIGHT 可能是参与自身免疫性炎症性疾病发展的关键细胞因子，LIGHT 靶向免疫疗法可能对这些疾病的治疗有用。
