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*
Center for Neurologic Diseases, Brigham and Womens Hospital and Harvard Medical School, Boston, MA 02115; and
Laboratory Service, Veterans Administration Health Care System, Palo Alto, CA 94304, and Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305
Experimental autoimmune encephalomyelitis (EAE) and other
organ-specific autoimmune diseases are induced by autoantigen-specific
Th1 cells. In contrast, transfer of autoantigen-reactive Th2 cells that
produce IL-4 and IL-10 can prevent and/or reverse EAE. The relative
roles of these two Th2 cytokines in the regulation of EAE has not been
evaluated. Utilizing IL-4 and IL-10 knockout mice deficient for these
cytokines and IL-10 and IL-4 transgenic mice overexpressing these
cytokines, we demonstrate that IL-10-deficient mice
(IL-10-/-) are more susceptible and develop a more severe
EAE when compared with IL-4-deficient mice (IL-4-/-) or
wild-type mice. T cells from IL-10-/- mice exhibit a
stronger Ag-specific proliferation, produce more proinflammatory
cytokines (IFN-
and TNF-
) when stimulated with an
encephalitogenic peptide, and induce very severe EAE upon transfer into
wild-type mice. In contrast, while IL-4 transgenic mice develop similar
disease compared with their nontransgenic littermates, mice transgenic
for IL-10 are completely resistant to the development of EAE. Taken
together, our data suggest that IL-10 plays a more critical role
in the regulation of EAE by regulating autopathogenic Th1
responses.
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