PMID- 19810097
OWN - NLM
STAT- MEDLINE
DCOM- 20091029
LR  - 20220410
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Linking)
VI  - 66
IP  - 3
DP  - 2009 Sep
TI  - Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple 
      sclerosis.
PG  - 390-402
LID - 10.1002/ana.21748 [doi]
AB  - 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.
FAU - Kebir, Hania
AU  - Kebir H
AD  - Neuroimmunology Research Unit, Center for Excellence in Neuromics, Montreal, 
      Quebec, Canada.
FAU - Ifergan, Igal
AU  - Ifergan I
FAU - Alvarez, Jorge Ivan
AU  - Alvarez JI
FAU - Bernard, Monique
AU  - Bernard M
FAU - Poirier, Josee
AU  - Poirier J
FAU - Arbour, Nathalie
AU  - Arbour N
FAU - Duquette, Pierre
AU  - Duquette P
FAU - Prat, Alexandre
AU  - Prat A
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-23)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Blood-Brain Barrier/immunology
MH  - Brain/*immunology
MH  - Cell Migration Assays
MH  - Cell Migration Inhibition/immunology
MH  - Central Nervous System/immunology
MH  - Encephalomyelitis, Autoimmune, Experimental/*blood/immunology
MH  - Female
MH  - Humans
MH  - In Vitro Techniques
MH  - Interferon-gamma/blood/*immunology
MH  - Interleukin-17/*immunology
MH  - Interleukin-23/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Multiple Sclerosis/*blood/immunology
MH  - Multiple Sclerosis, Relapsing-Remitting/blood/immunology
MH  - T-Lymphocytes/*immunology
MH  - Th1 Cells/immunology
MH  - Th2 Cells/immunology
EDAT- 2009/10/08 06:00
MHDA- 2009/10/30 06:00
CRDT- 2009/10/08 06:00
PHST- 2009/10/08 06:00 [entrez]
PHST- 2009/10/08 06:00 [pubmed]
PHST- 2009/10/30 06:00 [medline]
AID - 10.1002/ana.21748 [doi]
PST - ppublish
SO  - Ann Neurol. 2009 Sep;66(3):390-402. doi: 10.1002/ana.21748.