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?

Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal sur vival and plasticity during development and after injury. In the nervous sy stem, neurons are considered the major cellular sourer of BDNF. Wie demonst rate 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 p rotein 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 antib ody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in infl ammatory infiltrates in the brain of patients with acute disseminated encep halitis and multiple sclerosis. The results raise the possibility that in t he nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.