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?

被引:855
作者
Kerschensteiner, M
Gallmeier, E
Behrens, L
Leal, VV
Misgeld, T
Klinkert, WEF
Kolbeck, R
Hoppe, E
Oropeza-Wekerle, RL
Bartke, I
Stadelmann, C
Lassmann, H
Wekerle, H
Hohlfeld, R
机构
[1] Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany
[2] Max Planck Inst Neurobiol, Dept Neurobiochem, D-82152 Martinsried, Germany
[3] GSF Forschungszentrum Umwelt & Gesundheit, Div Environm Dermatol & Allergy, D-80802 Munich, Germany
[4] Tech Univ Munich, D-80802 Munich, Germany
[5] Boehringer Mannheim GmbH, D-82372 Penzberg, Germany
[6] Univ Vienna, Inst Clin Neuroimmunol, A-1090 Vienna, Austria
[7] Univ Vienna, Dept Neurol, A-1090 Vienna, Austria
关键词
neurotrophic factors; multiple sclerosis; autoimmunity; immunosuppressive therapy; neurodegeneration;
D O I
10.1084/jem.189.5.865
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 sourer of BDNF. Wie 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.
引用
收藏
页码:865 / 870
页数:6
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