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-Inducing Factor Prevent Experimental Autoimmune Encephalomyelitis1
*
Department of Immunology and
Rappaport Family Institute for Research in the Medical Sciences and Bruce Rappaport Faculty of Medicine, Haifa, Israel
Specific oligonucleotide primers were used to identify and isolate
IFN-
-inducing factor (IGIF) from the brain of rats with developing
experimental autoimmune encephalomyelitis (EAE), a T cell-mediated
autoimmune disease of the central nervous system that serves as a model
for multiple sclerosis. IGIF was highly transcribed in the brain at the
onset and during the course of active EAE. PCR products encoding rat
IGIF were used to generate the recombinant protein that was used to
induce anti-IGIF neutralizing Abs. These Abs significantly reduced
the production of IFN- by primed T cells proliferating in response
to their target myelin basic protein epitope and by Con A-activated T
cells from naive donors. When administered to rats during the
development of either active or transferred EAE, these Abs
significantly blocked the development of disease. Splenic T cells from
protected rats were cultured with the encephalitogenic myelin basic
protein epitope and evaluated for production of IL-4 and IFN-. These
cells, which proliferated, exhibited a profound increase in IL-4
production that was accompanied by a significant decrease in IFN-
and TNF-
production. Thus, we suggest that perturbation of the
Th1/Th2 balance toward Th2 cells is the mechanism underlying EAE
blockade by anti-IGIF immunotherapy.
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