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. (See: Sex Differences in AutoImmune Disease)
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-) precedes clinical attacks, and IFN- 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-.
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- were expressed in DeMyelinating lesions.
No Leukocyte expression of CCR3, CCR4, or six other Chemokines, or AntiInflammatory Cytokines IL-5, IL-10, IL-13, and Transforming Growth Factor-ß 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.
Communicated by David W. Talmage,
Univ of Colorado Health Sciences Center, Denver, CO, April 16, 1999 (received for review November 1, 1998)
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