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The Journal of Neuroscience, July 15, 2000, 20(14):5283-5291
Neuroprotection by Encephalomyelitis: Rescue of Mechanically
Injured Neurons and Neurotrophin Production by CNS-Infiltrating T and
Natural Killer Cells
H.
Hammarberg2,
O.
Lidman1,
C.
Lundberg1,
S. Y.
Eltayeb1,
A. W.
Gielen1,
S.
Muhallab1,
A.
Svenningsson1,
H.
Lindå3,
P. H.
van der
Meide4,
S.
Cullheim2,
T.
Olsson1, and
F.
Piehl1
1 Department of Medicine, Neuroimmunology Unit,
Karolinska Hospital, S171 76 Stockholm, Sweden,
2 Department of Neuroscience, Karolinska Institute, S171 77 Stockholm, Sweden, 3 Department of Neurology, Huddinge
Hospital, S141 86 Stockholm, Sweden, and 4 Central
Laboratory Animal Institute, Cytokine Biology Unit, Utrecht University,
3508 TD Utrecht, The Netherlands
In experimental autoimmune encephalomyelitis (EAE),
CD4+ self-reactive T cells target myelin components
of the CNS. However, the consequences of an autoaggressive T
cell response against myelin for neurons are currently unknown. We
herein demonstrate that EAE induced by active immunization with an
encephalitogenic myelin basic protein peptide dramatically
reduces the loss of spinal motoneurons after ventral root avulsion in
rats. Both brain-derived neurotophic factor (BDNF)- and neurotrophin-3
(NT-3)-like immunoreactivities were detected in mainly T and natural
killer (NK) cells in the spinal cord. In addition, very high levels of
BDNF, NT-3, and glial cell line-derived neurotrophic factor
mRNAs were present in T and NK cell populations infiltrating the CNS.
Interestingly, bystander recruited NK and T cells displayed similar or
higher neurotrophic factor levels compared with the EAE disease-driving encephalitogenic T cell population. High levels of tumor necrosis factor- (TNF-) and interferon- (IFN-) mRNAs were also
detected, and both these cytokines can be harmful to several types of
CNS cells, including neurons. However, treatment of embryonic
motoneuron cultures with TNF- or IFN- only had a deleterious
effect in cultures deprived of neurotrophic factors. These results
suggest that the potentially neurodamaging consequences of severe CNS inflammation are curbed by the production of several potent
neurotrophic factors in leukocytes.
Key words:
growth factors; neurotrophins; autoimmunity; axotomy; neurodegeneration; motoneuron
Copyright © 2000 Society for Neuroscience 0270-6474/00/20145283-09$05.00/0
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