A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity
A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity
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DOI：
10.1038/nm.3182
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发表时间：
2013-06-01
期刊：
影响因子：
82.9
通讯作者：
Fluegel, Alexander
中科院分区：
文献类型：
--
作者：
Lodygin, Dmitri;Odoardi, Francesca;Fluegel, Alexander
多发性硬化症是一种中枢神经系统(CNS)的自身免疫性疾病，当自我反应性T细胞进入大脑并在遇到其特定的神经抗原后被局部激活时，该疾病就会开始。与疾病相关的抗原相遇的时间和地点尚不清楚。在这里，我们将荧光标记的活化T细胞核因子(NFAT)与组蛋白H_2B结合起来，创建了一种广泛适用的分子传感器，用于T细胞激活的活体成像。在实验性自身免疫性脑脊髓炎中，我们报道了进入中枢神经系统的效应性T细胞在与软脑膜吞噬细胞短暂接触后被激活。在确定的疾病期间，激活过程延伸到中枢神经系统实质的深处，在那里细胞与小胶质细胞形成接触并招募吞噬细胞。我们表明，对于疾病的强度和持续时间来说，是临床前阶段的激活过程而不是确定的疾病期间的激活过程是必不可少的。
Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluorescently labeled nuclear factor of activated T cells (NFAT) with histone protein H2B to create a broadly applicable molecular sensor for intravital imaging of T cell activation. In experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, we report that effector T cells entering the CNS become activated after short contacts with leptomeningeal phagocytes. During established disease, the activation process is extended to the depth of the CNS parenchyma, where the cells form contacts with microglia and recruited phagocytes. We show that it is the activation processes during the preclinical phase rather than during established disease that are essential for the intensity and duration of the disease bout.