CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and theirligands MIP-1 alpha and IP-10 are expressed in demyelinating brain lesions

Multiple sclerosis (MS) is a T cell-dependent chronic inflammatory disease of the central nervous system, The role of chemokines in MS and its differe nt stages is uncertain. Recent data suggest a bias in expression of chemoki ne receptors by Th1 vs. Th2 cells; human Th1 clones express CXCR3 and CCR5 and Th2 clones express CCR3 and CCR4. Chemokine receptors expressed by Th1 cells may be important in MS, as increased interferon-gamma (IFN-gamma) pre cedes clinical attacks, and IFN-gamma injection induces disease exacerbatio ns. We found CXCR3(+) T cells increased in blood of relapsing-remitting MS, and both CCR5(+) and CXCR3(+) T cells increased in progressive MS compared with controls. Furthermore, peripheral blood CCR5(+) T cells secreted high levels of IFN-gamma, In the brain, the CCR5 ligand, MIP-1 alpha, was stron gly associated with microglia/macrophages, and the CXCR3 ligand, IP-10, was expressed by astrocytes in MS lesions but not unaffected white matter of c ontrol or MS subjects. Areas of plaque formation were infiltrated by CCR5-e xpressing and, to a lesser extent, CXCR3-expressing cells; Interleukin (IL) -18 and IFN-gamma were expressed in demyelinating lesions, No leukocyte exp ression of CCR3, CCR4, or six other chemokines, or anti-inflammatory cytoki nes IL-5, IL-10, IL-13, and transforming growth factor-beta was observed. T hus, chemokine receptor expression may be used for immunologic staging of M S and potentially for other chronic autoimmune/inflammatory processes such as rheumatoid arthritis, autoimmune diabetes, or chronic transplant rejecti on. Furthermore, these results provide a rationale for the use of agents th at block CCR5 and/or CXCR3 as a therapeutic approach in the treatment of MS .