Juedes Amy E, Rodrigo Evelyn, Togher Lisa, Glimcher Laurie H, von Herrath Matthias G
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121, USA.
J Exp Med. 2004 Apr 19;199(8):1153-62. doi: 10.1084/jem.20031873.
The T-box transcription factor T-bet is known to control lineage commitment and interferon-gamma production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter-lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-gamma, but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.
已知T盒转录因子T-bet可控制辅助性T细胞1（Th1）CD4淋巴细胞的谱系定向及γ干扰素的产生。我们在此报告，在病毒诱导的1型糖尿病（T1D）大鼠胰岛素启动子-淋巴细胞性脉络丛脑膜炎病毒（LCMV）转基因模型中，T-bet对于CD8淋巴细胞依赖性自身免疫性糖尿病（1型糖尿病 [T1D]）的发展至关重要。在缺乏T-bet的情况下，自身攻击性（抗LCMV）CD8淋巴细胞数量减少，产生的γ干扰素减少，但与对照组相比，白细胞介素-2增加。进一步分析表明，T-bet内在地控制抗病毒效应/记忆CD8淋巴细胞的产生，但不控制其凋亡、维持或二次扩增。这一观察结果为治疗T1D和其他自身免疫性疾病提供了一个治疗机会。
