Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 10, Pages 5909-5913Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803418
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Funding
- Nationai Multiple Sclerosis Society of the United States
- Swiss Multiple Sclerosis Society
- Bern University Research Foundation
- Fondation poor la Recherche Medicale
- Association pour la Recherche sur la Sclerose en Plaques
- National Multiple Sclerosis Society
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The humanized anti-alpha(4) integrin Ab Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis. Natalizumab is thought to exert its therapeutic efficacy by blocking the alpha(4) integrin-mediated binding of circulating immune cells to the blood-brain barrier (BBB). As alpha(4) integrins control other immunological processes, natalizumab may, however, execute its beneficial effects elsewhere. By means of intravital microscopy we demonstrate that natalizumab specifically inhibits the firm adhesion but not the rolling or capture of human T cells on the inflamed BBB in mice with acute experimental autoimmune encephalomyelitis (EAE). The efficiency of natalizumab to block T cell adhesion to the inflamed BBB was found to be more effective in EAE than in acute systemic TNF-alpha-induced inflammation. Our data demonstrate that alpha(4) integrin-mediated adhesion of human T cells to the inflamed BBB during EA-E is efficiently blocked by natalizumab and thus provide the first direct in vivo proof of concept of this therapy in multiple sclerosis. The Journal of Immunology, 2009, 182: 5909-5913.
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