Cutting edge: Natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis

Coisne, Caroline; Mao, Wenxian; Engelhardt, Britta (2009). Cutting edge: Natalizumab blocks adhesion but not initial contact of human T cells to the blood-brain barrier in vivo in an animal model of multiple sclerosis. Journal of immunology, 182(10), pp. 5909-13. Bethesda, Md.: American Association of Immunologists 10.4049/jimmunol.0803418

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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 EAE is efficiently blocked by natalizumab and thus provide the first direct in vivo proof of concept of this therapy in multiple sclerosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Coisne, Caroline Marie and Engelhardt, Britta

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

04 May 2014 23:23

Publisher DOI:

10.4049/jimmunol.0803418

PubMed ID:

19414741

Web of Science ID:

000265899800006

URI:

https://boris.unibe.ch/id/eprint/32144 (FactScience: 197071)

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