An essential regulatory role for macrophage migration inhibitory factor in T-cell activation
An essential regulatory role for macrophage migration inhibitory factor in T-cell activation
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DOI：
10.1073/pnas.93.15.7849
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发表时间：
1996-07-23
影响因子：
11.1
通讯作者：
Bucala, R
中科院分区：
文献类型：
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作者：
Bacher, M;Metz, CN;Bucala, R
被称为巨噬细胞迁移抑制因子（MIF）的蛋白质是最早被发现的细胞因子之一，并且在30年前被描述为抑制体外巨噬细胞随机迁移的T细胞衍生因子。一个更广泛的作用，为MIF最近出现的结果，研究表明，它是从垂体前叶在体内释放。MIF也是第一个被鉴定为在糖皮质激素刺激时从单核细胞/巨噬细胞分泌的蛋白质。一旦被释放，MIF的作用是“推翻”或反调节糖皮质激素对巨噬细胞细胞因子产生的抑制作用。我们在此报告，MIF发挥重要作用。在有丝分裂或抗原刺激诱导的T细胞活化中的调节作用。活化的T细胞产生MIF，中和性抗MIF抗体在体外抑制T细胞增殖和白细胞介素2产生，并在体内抑制抗原驱动的T细胞活化和抗体产生。T细胞还响应于糖皮质激素刺激而释放MIF，并且MIF起作用以克服糖皮质激素对T细胞增殖以及白细胞介素2和干扰素γ产生的抑制。这些研究表明，MIF与糖皮质激素共同控制T细胞活化，并在抗原特异性免疫应答中为MIF分配了先前未被怀疑但至关重要的作用。
The protein known as macrophage migration inhibitory factor (MIF) was one of the first cytokines to be discovered and was described 30 years ago to be a T-cell-derived factor that inhibited the random migration of macrophages in vitro. A much broader role for MIF has emerged recently as a result of studies that have demonstrated it to be released from the anterior pituitary gland in vivo. MIF also is the first protein that has been identified to be secreted from monocytes/macrophages upon glucocorticoid stimulation. Once released, MIF acts to ''override'' or counter-regulate the suppressive effects of glucocorticoids on macrophage cytokine production. We report herein that MIF plays an important. regulatory role in the activation of T cells induced by mitogenic or antigenic stimuli. Activated T cells produce MIF and neutralizing anti-MIF antibodies inhibit T-cell proliferation and interleukin 2 production in vitro, and suppress antigen-driven T-cell activation and antibody production in vivo. T cells also release MIF in response to glucocorticoid stimulation and MIF acts to override glucocorticoid inhibition of T-cell proliferation and interleukin 2 and interferon gamma production. These studies indicate that MIF acts in concert with glucocorticoids to control T-cell activation and assign a previously unsuspected but critical role for MIF in antigen-specific immune responses.