Brain, Vol. 123, No. 9, 1874-1882,
September 2000
© 2000 Oxford University Press
Aberrant T cell migration toward RANTES and MIP-1
in patients with multiple sclerosis
Overexpression of chemokine receptor CCR5
.
1 Multiple Sclerosis Research Laboratory, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center and 2 Department of Immunology, Baylor College of Medicine, Houston, Texas, USA
Correspondence to:
Dr Jingwu Zhang, Department of Neurology, Baylor College of Medicine, 6501 Fannin Street, NB302, Houston, TX 77030, USA E-mail: jzang{at}bcm.tmc.edu
Trafficking of inflammatory T cells into the central nervous system (CNS) plays an important role in the pathogenesis of multiple sclerosis. The directional migratory ability of peripheral T cells is associated with interactions of chemokines with their receptors expressed on T cells. In this study, transmigration of peripheral T cells toward a panel of chemokines was examined in patients with multiple sclerosis and healthy individuals using Boyden chemotactic transwells. A significantly increased migratory rate preferentially toward RANTES and MIP-1
, but not other chemokines, was found in T cells obtained from multiple sclerosis patients as opposed to healthy individuals (P < 0.001). The migratory T-cell populations represented predominantly Th1/Th0 cells while non-migratory T cells were enriched for Th2-like cells. The study demonstrated further that aberrant migration of multiple sclerosis-derived T cells toward RANTES and MIP-1 resulted from overexpression of their receptors (CCR5) and could be blocked by anti-CCR5 antibodies. These findings have important implications for our understanding of the mechanism underlying aberrant T cell trafficking in multiple sclerosis.
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