title: Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis.
abstract: OBJECTIVE
  Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR).
  
  
  METHODS
  A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew.
  
  
  RESULTS
  Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1.
  
  
  CONCLUSIONS
  This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.
authors: Université de Bourgogne and CHU Dijon le Bocage, Dijon, France.
authors: Maxime
authors: M
authors: Samson
authors: Sylvain
authors: S
authors: Audia
authors: Jennifer
authors: J
authors: Fraszczak
authors: Malika
authors: M
authors: Trad
authors: Paul
authors: P
authors: Ornetti
authors: Daniela
authors: D
authors: Lakomy
authors: Marion
authors: M
authors: Ciudad
authors: Vanessa
authors: V
authors: Leguy
authors: Sabine
authors: S
authors: Berthier
authors: Julien
authors: J
authors: Vinit
authors: Patrick
authors: P
authors: Manckoundia
authors: Jean-Francis
authors: JF
authors: Maillefert
authors: Jean-François
authors: JF
authors: Besancenot
authors: Serge
authors: S
authors: Aho-Glele
authors: Nils Olivier
authors: NO
authors: Olsson
authors: Bernard
authors: B
authors: Lorcerie
authors: Loïc
authors: L
authors: Guillevin
authors: Luc
authors: L
authors: Mouthon
authors: Philippe
authors: P
authors: Saas
authors: Andrew
authors: A
authors: Bateman
authors: Laurent
authors: L
authors: Martin
authors: Nona
authors: N
authors: Janikashvili
authors: Nicolas
authors: N
authors: Larmonier
authors: Bernard
authors: B
authors: Bonnotte
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D013700:Giant Cell Arteritis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology*; D011111:Polymyalgia Rheumatica / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B