Fiche du document
- doi: 10.1212/NXI.0000000000000401
- issn: 2332-7812
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1212/NXI.0000000000000401
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/29075657
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pissn/2332-7812
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_4147F114C8176
info:eu-repo/semantics/openAccess , CC BY-NC-ND 4.0 , https://creativecommons.org/licenses/by-nc-nd/4.0/
Sujets proches
Thymus-dependent lymphocytes Thymus-derived cells T lymphocytes Thymus-dependent cellsCiter ce document
A. Mathias et al., « Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate. », Serveur académique Lausannois, ID : 10.1212/NXI.0000000000000401
Métriques
Partage / Export
Résumé
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.