Objective: T helper (Th)1 and Th17 lymphocytes are involved in experimental autoimmune encephalomyelitis, the model of multiple sclerosis (MS). We characterized the Th1/Th17 cell populations in peripheral blood (PB), their interferon (IFN) receptor expression, and their sensitivity to IFN-β in MS patients. Methods: The study included untreated patients with active (AMS; n = 30) and inactive MS (IMS; n = 32), and healthy subjects (HS; n = 22). We measured intracellular cytokine expression, interleukin (IL)-17-producing myelin basic protein (MBP)-stimulated PB lymphocytes, surface IFN type I receptor chain1 (IFN-αR1) expression, IFN-β-dependent signal transducer, and activator of transcription (STAT) 1 phosphorylation and apoptosis of anti-CD3 monoclonal antibody-stimulated PB lymphocytes. Results: The percentage of Th17 cells increased around 7-fold in AMS patients compared with IMS or HS, but there was no change in Th1 cells. Th17 cells in AMS patients were MBP-specific. The longitudinal follow-up of 18 MS patients shifting between AMS and IMS showed that the percentage of Th17 but not Th1 cells always increased in AMS. IFN-αR1 expression, IFN-β-induced STAT1 activation and apoptosis were significantly greater in Th17 than Th1 cells. IFN-αR1 expression and IFN-β-dependent STAT1 activation progressively increased in-vitro with a highly significant positive correlation only in developing Th17 but not in Th0 or Th1 cells. Interpretation: We present evidence of an expansion of peripheral Th17 cells, a Th subset that can infiltrate brain parenchyma and damage cells, associated with disease activity in MS. The higher IFN-αR1 level expressed by Th17 compared with Th1 cells might make them a selective target for IFN-β therapy.

T helper 17 cells expand in multiple sclerosis and are inhibited by interferon-β

DURELLI, Luca;CONTI, Laura;CLERICO, Marinella;NOVELLI, Francesco
2009

Abstract

Objective: T helper (Th)1 and Th17 lymphocytes are involved in experimental autoimmune encephalomyelitis, the model of multiple sclerosis (MS). We characterized the Th1/Th17 cell populations in peripheral blood (PB), their interferon (IFN) receptor expression, and their sensitivity to IFN-β in MS patients. Methods: The study included untreated patients with active (AMS; n = 30) and inactive MS (IMS; n = 32), and healthy subjects (HS; n = 22). We measured intracellular cytokine expression, interleukin (IL)-17-producing myelin basic protein (MBP)-stimulated PB lymphocytes, surface IFN type I receptor chain1 (IFN-αR1) expression, IFN-β-dependent signal transducer, and activator of transcription (STAT) 1 phosphorylation and apoptosis of anti-CD3 monoclonal antibody-stimulated PB lymphocytes. Results: The percentage of Th17 cells increased around 7-fold in AMS patients compared with IMS or HS, but there was no change in Th1 cells. Th17 cells in AMS patients were MBP-specific. The longitudinal follow-up of 18 MS patients shifting between AMS and IMS showed that the percentage of Th17 but not Th1 cells always increased in AMS. IFN-αR1 expression, IFN-β-induced STAT1 activation and apoptosis were significantly greater in Th17 than Th1 cells. IFN-αR1 expression and IFN-β-dependent STAT1 activation progressively increased in-vitro with a highly significant positive correlation only in developing Th17 but not in Th0 or Th1 cells. Interpretation: We present evidence of an expansion of peripheral Th17 cells, a Th subset that can infiltrate brain parenchyma and damage cells, associated with disease activity in MS. The higher IFN-αR1 level expressed by Th17 compared with Th1 cells might make them a selective target for IFN-β therapy.
65(5)
499
509
L Durelli; L Conti; M Clerico; D Boselli; G Contessa; P Ripellino; B Ferrero; P Eid; F Novelli
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/57442
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