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  • 标题:CCR5+ and CXCR3+ T cells are increased in multiple sclerosis and their ligands MIP-1α and IP-10 are expressed in demyelinating brain lesions
  • 本地全文:下载
  • 作者:Konstantin E. Balashov ; James B. Rottman ; Howard L. Weiner
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1999
  • 卷号:96
  • 期号:12
  • 页码:6873-6878
  • DOI:10.1073/pnas.96.12.6873
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Multiple sclerosis (MS) is a T cell-dependent chronic inflammatory disease of the central nervous system. The role of chemokines in MS and its different stages is uncertain. Recent data suggest a bias in expression of chemokine 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}) precedes clinical attacks, and IFN-{gamma} injection induces disease exacerbations. 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, was strongly associated with microglia/macrophages, and the CXCR3 ligand, IP-10, was expressed by astrocytes in MS lesions but not unaffected white matter of control or MS subjects. Areas of plaque formation were infiltrated by CCR5-expressing and, to a lesser extent, CXCR3-expressing cells; Interleukin (IL)-18 and IFN-{gamma} were expressed in demyelinating lesions. No leukocyte expression of CCR3, CCR4, or six other chemokines, or anti-inflammatory cytokines IL-5, IL-10, IL-13, and transforming growth factor-{beta} was observed. Thus, chemokine receptor expression may be used for immunologic staging of MS and potentially for other chronic autoimmune/inflammatory processes such as rheumatoid arthritis, autoimmune diabetes, or chronic transplant rejection. Furthermore, these results provide a rationale for the use of agents that block CCR5 and/or CXCR3 as a therapeutic approach in the treatment of MS.
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