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Vol. 305, Issue 1, 70-77, April 2003
Laboratory of Transplantation Immunology, Department of Innovative
Surgery, National Research Institute for Child Health and Development,
Tokyo, Japan
Experimental autoimmune encephalomyelitis (EAE) is a T-cell-dependent
autoimmune disease that reproduces the inflammatory demyelinating
pathology of multiple sclerosis (MS). We investigated the efficacy and
mechanism of immunosuppression against EAE by administering
2-amino-[2-(4-octylphenyl) ethyl]-1,3-propanediol hydrochloride
(FTY720) in Lewis rats immunized with myelin basic protein
together with complete Freund's adjuvant. FTY720 treatment almost
completely protected the rats against disease. The protection by FTY720
was associated with a dramatic reduction in the number of lymphocytes
staining for T-cell receptors in the spinal cord as examined by
immunohistochemistry. The mRNA expression of Th1 cytokines interleukin
(IL)-2, IL-6, and interferon-
in the spinal cord was also
reduced dramatically as assessed by reverse-transcription polymerase
chain reaction. Furthermore, lymphocytes isolated from the spleen of
FTY720-treated rats were transferred into naive recipient rats against
EAE manifestation by reducing both disease incidence and clinical
score. These results suggested that the protective anti-inflammatory
effect of treatment with FTY720 was, to a large extent, due to the
inhibition of encephalitogenic T-cell responses and/or their migration
into the central nervous system and may be a potential candidate for
use in treating patients with MS.
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