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Brief Definitive Reports |



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.
Key Words: neurotrophic factors multiple sclerosis autoimmunity immunosuppressive therapy neurodegeneration
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.
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