Modulation of experimental autoimmune encephalomyelitis: effect of alteredpeptide ligand on chemokine and chemokine receptor expression

Experimental autoimmune encephalomyelitis (EAE) is a T helper 1 (Th1) cell mediated demyelinating disease and the principal animal model for multiple sclerosis. Spinal cords from SJL mice primed with proteolipid protein pepti de 139-151 (pPLP) expressed the chemokines RANTES, MCP-1, MIP-2, KC, MZP-1 alpha, MIP-1 beta, Mig, and fractalkine. We also identified IP-10 in these samples and described a sequence polymorphism in this transcript. Chemokine expression was specific for tissues of the central nervous system. MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical scor e. Chemokine receptor expression generally correlated with ligand expressio n. pPLP-primed mice expressed the Th1-associated markers CCR5 and CXCR3 on mononuclear cells. In addition, cells expressing CCR1, CCR2, CCRS, CCR4, CC R8, and CXCR2 were detected. Here we demonstrate that altered peptide ligan d (APL)-induced protection from EAE was accompanied by modulation of chemok ine and chemokine receptor expression. Spinal cord tissue sections from APL -protected mice showed greatly reduced levels of all chemokines and of CCR1 , CCRS, CCR8, CXCR2 and CXCR3. The Th2-associated chemokine receptors CCR3 and CCR4 were found in protected mice, supporting the hypothesis that Th1 b ut not Th2 cells are down-regulated by APL treatment. This report concludes that chemokines and chemokine receptors can be useful tools to follow modu lation of autoimmune disease. (C) 2000 Elsevier Science B.V. All rights res erved.