International Immunology, Vol 9, 1837-1847, Copyright © 1997 by Oxford University Press
A Inoue, CS Koh, M Yamazaki, M Ichikawa, M Isobe, Y Ishihara, H Yagita and BS Kim
We examined the role of leukocyte function-associated antigen (LFA)-1 and
its counter-receptor intercellular adhesion molecule (ICAM)-1, one of the
most important pairs of adhesion molecules, in the development of Theiler's
murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD).
Immunohistochemical study showed hyper-expression of ICAM-1 on vascular
endothelial cells and expression of LFA-1 on mononuclear infiltrating cells
in the spinal cords of TMEV-infected mice. Treatment with mAb to ICAM-1
and/or LFA-1 molecules resulted in significant suppression of the
development of demyelinating disease, both clinically and histologically,
with down-regulation in the CNS of the respective adhesion molecules after
treatment. In mice treated with these mAb, the specific delayed-type
hypersensitivity and T cell proliferative responses for TMEV were
decreased. The production of tumor necrosis factor-alpha and IFN-gamma in
spleen cells was also decreased, but IL-4 production remained unchanged.
These data suggest that ICAM-1/LFA-1 interaction is critically involved in
the pathogenesis of TMEV-IDD and that antibodies to these adhesion
molecules could be a novel therapeutic approach to the treatment of
demyelinating diseases such as human multiple sclerosis.
ARTICLES
Anti-adhesion molecule therapy in Theiler's murine encephalomyelitis virus-induced demyelinating disease
Third Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
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