Preferential recruitment of interferon‐γ–expressing TH17 cells in multiple sclerosis

Annals of Neurology - Tập 66 Số 3 - Trang 390-402 - 2009
Hania Kébir1, Igal Ifergan1, Jorge I. Alvarez1, Monique Bernard1, Josée Poirier2, Nathalie Arbour1, Pierre Duquette2, Alexandre Prat2,1
1Neuroimmunology Research Unit, Center for Excellence in Neuromics, Montreal, Quebec, Canada
2Multiple Sclerosis Clinic, University of Montreal Hospital Center–Notre Dame Hospital, Montreal, Quebec, Canada

Tóm tắt

AbstractObjectiveThere 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).MethodsHuman TH17 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.ResultsWe 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 TH17‐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.InterpretationOur 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. Ann Neurol 2009;66:390–402

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Annals of Neurology

Tập 66 Số 3

390-402

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