IL-12 dependent/IFN gamma independent expression of CCR5 by myelin-reactive T cells correlates with encephalitogenicity.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to multiple sclerosis (MS). It is induced in mice by the transfer of myelin-reactive T cells. Here we demonstrate that IL-12 stimulates myelin-reactive T cells to up-regulate the beta-chemokine receptor, CCR5, in correlation with the acquisition of central nervous system-infiltrating and encephalitogenic properties. These effects of IL-12 are IFN gamma-independent. The CCR5 ligands, RANTES and MIP-1 alpha, are expressed in the spinal cords of mice at EAE onset. Our results suggest that reagents that block CCR5/beta-chemokine interactions and/or antagonize IL-12 might be useful for treatment of autoimmune demyelination.