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.
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1 March 1999
Brief Definitive Report|
March 01 1999
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?
Martin Kerschensteiner,
Martin Kerschensteiner
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Eike Gallmeier,
Eike Gallmeier
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Lüder Behrens,
Lüder Behrens
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Vivian Vargas Leal,
Vivian Vargas Leal
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Thomas Misgeld,
Thomas Misgeld
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Wolfgang E.F. Klinkert,
Wolfgang E.F. Klinkert
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Roland Kolbeck,
Roland Kolbeck
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Edmund Hoppe,
Edmund Hoppe
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Rosa-Laura Oropeza-Wekerle,
Rosa-Laura Oropeza-Wekerle
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Ilse Bartke,
Ilse Bartke
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Christine Stadelmann,
Christine Stadelmann
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Hans Lassmann,
Hans Lassmann
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Hartmut Wekerle,
Hartmut Wekerle
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Reinhard Hohlfeld
Reinhard Hohlfeld
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
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Martin Kerschensteiner
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Eike Gallmeier
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Lüder Behrens
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Vivian Vargas Leal
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Thomas Misgeld
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Wolfgang E.F. Klinkert
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Roland Kolbeck
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Edmund Hoppe
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Rosa-Laura Oropeza-Wekerle
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Ilse Bartke
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Christine Stadelmann
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Hans Lassmann
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Hartmut Wekerle
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Reinhard Hohlfeld
From the *Department of Neuroimmunology and the ‡Department of Neurobiochemistry, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany; the §Division of Environmental Dermatology and Allergy, Forschungszentrum für Umwelt und Gesundheit (GSF) and Technical University Munich, D-80802 Munich, Germany; ‖Boehringer-Mannheim, D-82372 Penzberg, Germany; the ¶Institute of Neurology, University of Vienna, A-1090 Vienna, Austria; and the **Institute for Clinical Neuroimmunology and Department of Neurology, Ludwig Maximilians University, D-81366 Munich, Germany
Address correspondence to Reinhard Hohlfeld, Department of Neuroimmunology, Max Planck Institute for Neurobiology, Am Klopferspitz 18A, D-82152 Martinsried, Germany. Phone: 49-89-7095-4780; Fax: 49-89-7095-4782; E-mail: [email protected]
The Institute for Clinical Neuroimmunology is supported by the Hermann und Lilly Schilling-Foundation and Max Planck-Society. This project was further supported by the Deutsche Forschungsgemeinschaft (SFB 217, C13), Hertie-Stiftung (GHS 339/95), and European Community (BMH4-CT96-0893: Immunoregulatory aspects of T cell autoimmunity in multiple sclerosis). R.L. Oropeza-Wekerle was supported by GSF FE-72121 and the Klinik and Poliklinik für Dermatologie and Allergologie, Technical University of Munich. This study is part of the M.D. theses of M. Kerschensteiner and E. Gallmeier.
Received:
July 24 1998
Revision Received:
December 21 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (5): 865–870.
Article history
Received:
July 24 1998
Revision Received:
December 21 1998
Citation
Martin Kerschensteiner, Eike Gallmeier, Lüder Behrens, Vivian Vargas Leal, Thomas Misgeld, Wolfgang E.F. Klinkert, Roland Kolbeck, Edmund Hoppe, Rosa-Laura Oropeza-Wekerle, Ilse Bartke, Christine Stadelmann, Hans Lassmann, Hartmut Wekerle, Reinhard Hohlfeld; 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? . J Exp Med 1 March 1999; 189 (5): 865–870. doi: https://doi.org/10.1084/jem.189.5.865
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