Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation?

Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation?
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DOI:
10.1084/jem.189.5.865
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发表时间:
1999-03-01
影响因子:
15.3
通讯作者:
Hohlfeld, R
Hohlfeld, R
中科院分区:
医学1区
文献类型:
--
作者:
Kerschensteiner, M;Gallmeier, E;Behrens, L;Leal, V V;Misgeld, T;Klinkert, W E;Kolbeck, R;Hoppe, E;Oropeza-Wekerle, R L;Bartke, I;Stadelmann, C;Lassmann, H;Wekerle, H;Hohlfeld, R

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脑源性神经营养因子(BDNF)对发育和损伤后神经元的存活和可塑性有重要影响。在神经系统中,神经元被认为是BDNF的主要细胞来源。此外,我们在这里证明,活化的人T细胞、B细胞和单核细胞在体外分泌生物活性BDNF。值得注意的是,在辅助性T细胞(Th)1-和th2型CD4+ T细胞系中,髓鞘自身抗原(如髓鞘碱性蛋白或髓鞘少突胶质细胞糖蛋白)特异性,BDNF的产生在抗原刺激下增加。免疫细胞分泌的BDNF具有生物活性,支持体外神经元存活。应用抗BDNF单克隆抗体和多克隆抗血清,在急性播散性脑炎和多发性硬化症患者的脑内炎症浸润中证实了BDNF的免疫反应性。这些结果提出了在神经系统中,炎症浸润具有神经保护作用的可能性,这可能会限制非选择性免疫疗法的成功。
Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4+ T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.