Abstract
Multiple Sclerosis (MS) is an autoimmune-mediated chronic demyelinating disease of the central nervous system. The role of CD4+ T helper T cells in the pathogenesis of this disease is established. CD4+ T cells comprise various Th subsets, including Th1 and Th17 cells. The contributution of each T cell subset to MS pathology is not fully elucidated. As each Th subset have characteristic chemokine receptor expression patterns, we compared the frequency of various inflammatory chemokine receptor positive Th cells in peripheral blood with those from cerebrospinal fluid (CSF) for each MS patient. CCR2+CCR5+CD4+ T cells were selectively enriched in the CSF of MS patients but not in other neurological diseases. Peripheral CCR2+CCR5+CD4+ Tcells produced both IFN-γ and IL-17, expressed Matrix Metalloproteinase-9 (MMP9) and Osteopontin, and transmigrated in an in vitro blood brain barrier model more efficiently than other Th cells, suggesting a BBB-invading mechanism and an important role in the relapse of MS. This study illustrates the potential of method in which examining the combination of chemokine receptors could reveal a Th subset with disease-relevant function.
