Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_4147F114C817
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate.
Journal
Neurology: Neuroimmunology & Neuroinflammation
Author(s)
Mathias A., Perriot S., Canales M., Blatti C., Gaubicher C., Schluep M., Engelhardt B., Du Pasquier R.
ISSN
2332-7812 (Print)
ISSN-L
2332-7812
Publication state
Published
Issued date
11/2017
Peer-reviewed
Oui
Volume
4
Number
6
Pages
e401
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile.
We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36-48 months. The ex vivo expression of CNS-related integrins (α4β1 and αL subunit of LFA-1) and the gut-related integrin (α4β7) was assessed using flow cytometry on CD4(+) and CD8(+) T cells. The adhesion profiles of CD3(+) T cells to specific integrin ligands (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and mucosal vascular addressin cell adhesion molecule-1 [MAdCAM-1]) were measured in vitro before and after 12 and 36-48 months.
NTZ decreased the frequency of α4β1(+) and α4β7(+) integrin expressing T cells and the binding of these cells to VCAM-1 and MAdCAM-1, respectively. After 12 months, DMF induced a decreased frequency of αL(high)CD4(+) T cells combined with reduced binding to ICAM-1. By contrast, with FTY, there was a doubling of the frequency of α4β1(+) and αL(high), but a decreased frequency of α4β7(+) T cells. Strikingly, the binding of α4β1(+), α4β7(+), and to a lesser extent of αL(high) T cells to VCAM-1, MAdCAM-1, and ICAM-1, respectively, was decreased at month 12 under FTY treatment. The presence of manganese partially restored the binding of these T cells to VCAM-1 in vitro, suggesting that FTY interferes with integrin activation.
In addition to NTZ, DMF and FTY but not other tested DMTs may also decrease T-cell-mediated immune surveillance of the CNS. Whether this mechanism may contribute to the onset of CNS opportunistic infections remains to be shown.
Pubmed
Open Access
Yes
Create date
09/11/2017 18:53
Last modification date
27/09/2023 5:58
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