Aberrant T cell migration toward RANTES and MIP-1 alpha in patients with multiple sclerosis - Overexpression of chemokine receptor CCR5

Trafficking of inflammatory T cells into the central nervous system (CNS) p lays an important role in the pathogenesis of multiple sclerosis, The direc tional migratory ability of peripheral T cells is associated with interacti ons of chemokines with their receptors expressed on T cells. In this study, transmigration of peripheral T cells toward a panel of chemokines was exam ined in patients with multiple sclerosis and healthy individuals using Boyd en chemotactic transwells. A significantly increased migratory rate prefere ntially toward RANTES and MIP-la, but not other chemokines, was found in T cells obtained from multiple sclerosis patients as opposed to healthy indiv iduals (P < 0.001), The migratory T-cell populations represented predominan tly Th1/Th0 cells while non-migratory T cells were enriched for Th2-like ce lls. The study demonstrated further that aberrant migration of multiple scl erosis-derived T cells toward RANTES and MIP-1 alpha resulted from overexpr ession of their receptors (CCR5) and could be blocked by anti-CCR5 antibodi es. These findings have important implications for our understanding of the mechanism underlying aberrant T cell trafficking in multiple sclerosis.