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) 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-1alpha, 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 alpha 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.
Zang
Y C
YC
Multiple Sclerosis Research Laboratory, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Samanta
A K
AK
Halder
J B
JB
Hong
J
J
Tejada-Simon
M V
MV
Rivera
V M
VM
Zhang
J Z
JZ
D002465:Cell Movement / Q000502:physiology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5