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Ann Neurol. 2009 Sep;66(3):390-402. doi: 10.1002/ana.21748.

Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis.

Author information

1
Neuroimmunology Research Unit, Center for Excellence in Neuromics, Montreal, Quebec, Canada.

Abstract

OBJECTIVE:

There is substantial evidence supporting the role of interferon (IFN)-gamma-producing T helper (T(H)) 1 and interleukin (IL)-17-expressing T(H)17 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-gamma-expressing T(H)17 lymphocytes in MS and EAE, and study their recruitment into the central nervous system (CNS).

METHODS:

Human T(H)17 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 T(H)17 phenotype, with a subpopulation of cells simultaneously expressing IFN-gamma and IL-17. We note that lymphocytes obtained from the blood of relapsing MS patients have an increased propensity to expand into IFN-gamma-producing T(H)17 cells and identify numerous T lymphocytes coexpressing IL-17 and IFN-gamma in brain tissue of MS patients. We also find lymphocytes expressing both the T(H)1- and the T(H)17-associated transcription factors ROR gamma t and T-bet, in situ and in vitro. We further provide in vitro and in vivo evidence that IFN-gamma(+) T(H)17 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-gamma(+) T(H)17 lymphocytes in the pathology of MS and EAE and their preferential recruitment into the CNS during inflammatory events.

PMID:
19810097
DOI:
10.1002/ana.21748
[Indexed for MEDLINE]

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