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, 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

Research output: Contribution to journalArticlepeer-review

929 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)865-870
Number of pages6
JournalJournal of Experimental Medicine
Volume189
Issue number5
DOIs
StatePublished - 1 Mar 1999
Externally publishedYes

Keywords

  • Autoimmunity
  • Immunosuppressive therapy
  • Multiple sclerosis
  • Neurodegeneration
  • Neurotrophic factors

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