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 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.
Kerschensteiner
M
M
Department of Neuroimmunology, Max Planck Institute for Neurobiology, D-82152 Martinsried, Germany.
Gallmeier
E
E
Behrens
L
L
Leal
V V
VV
Misgeld
T
T
Klinkert
W E
WE
Kolbeck
R
R
Hoppe
E
E
Oropeza-Wekerle
R L
RL
Bartke
I
I
Stadelmann
C
C
Lassmann
H
H
Wekerle
H
H
Hohlfeld
R
R
D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001927:Brain Diseases / Q000276:immunology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D004660:Encephalitis / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D019636:Neurodegenerative Diseases / Q000276:immunology; D009836:Oligodendroglia / Q000276:immunology; D012333:RNA, Messenger / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D001324:Autoantigens; D019208:Brain-Derived Neurotrophic Factor; D006023:Glycoproteins; D004676:Myelin Basic Protein; D012333:RNA, Messenger