Preferential recruitment of interferon-γ-expressing TH17 cells in multiple sclerosis

Hania Kebir, Igal Ifergan, Jorge Ivan Alvarez, Monique Bernard, Josée Poirier, Nathalie Arbour, Pierre Duquette, Alexandre Prat*

*Corresponding author for this work

Research output: Contribution to journalArticle

329 Scopus citations

Abstract

Objective: There is substantial evidence supporting the role of interferon (IFN)-γ-producing T helper (TH) 1 and interleukin (IL)-17-expressing TH17 lymphocytes in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). However, to date little is known about the potential cooperative interplay between these 2 cytokines. In the current study, we sought to evaluate the frequency of IFN-γ-expressing TH17 lymphocytes in MS and EAE, and study their recruitment into the central nervous system (CNS). Methods: Human T H17 lymphocytes were expanded in vitro from the blood of healthy controls and relapsing MS patients using IL-23. Immune cell migration to the CNS was assessed in vitro with primary cultures of human blood-brain barrier (BBB)-derived endothelial cells, and in vivo in EAE mice. Results: We demonstrate that in response to IL-23, human memory lymphocytes expand into a TH17 phenotype, with a subpopulation of cells simultaneously expressing IFN-γ and IL-17. We note that lymphocytes obtained from the blood of relapsing MS patients have an increased propensity to expand into IFN-γ - producing TH17 cells and identify numerous T lymphocytes coexpressing IL-17 and IFN-γ in brain tissue of MS patients. We also find lymphocytes expressing both the TH1-and the T H17-associated transcription factors RORγt and T-bet, in situ and in vitro. We further provide in vitro and in vivo evidence that IFN-γ+ TH17 lymphocytes preferentially cross the human BBB and accumulate in the CNS of mice during the effector phase of EAE. Interpretation: Our data underscore the involvement of IFN-γ+ TH17 lymphocytes in the pathology of MS and EAE and their preferential recruitment into the CNS during inflammatory events.

Original languageEnglish (US)
Pages (from-to)390-402
Number of pages13
JournalAnnals of neurology
Volume66
Issue number3
DOIs
StatePublished - Oct 22 2009

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Kebir, H., Ifergan, I., Alvarez, J. I., Bernard, M., Poirier, J., Arbour, N., Duquette, P., & Prat, A. (2009). Preferential recruitment of interferon-γ-expressing TH17 cells in multiple sclerosis. Annals of neurology, 66(3), 390-402. https://doi.org/10.1002/ana.21748