J. Exp. Med., Volume 189, Number 5, March 1, 1999 865-870

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?

By 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,^* and 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

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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