Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis

Maxime Samson, Sylvain Audia, Jennifer Fraszczak, Malika Trad, Paul Ornetti, Daniela Lakomy, Marion Ciudad, Vanessa Leguy, Sabine Berthier, Julien Vinit, Patrick Manckoundia, Jean Francis Maillefert, Jean François Besancenot, Serge Aho-Glele, Nils Olivier Olsson, Bernard Lorcerie, Loïc Guillevin, Luc Mouthon, Philippe Saas, Andrew BatemanLaurent Martin, Nona Janikashvili, Nicolas Larmonier, Bernard Bonnotte

Research output: Contribution to journalArticle

107 Scopus citations

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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)3788-3798
Number of pages11
JournalArthritis and Rheumatism
Volume64
Issue number11
DOIs
StatePublished - Nov 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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    Samson, M., Audia, S., Fraszczak, J., Trad, M., Ornetti, P., Lakomy, D., Ciudad, M., Leguy, V., Berthier, S., Vinit, J., Manckoundia, P., Maillefert, J. F., Besancenot, J. F., Aho-Glele, S., Olsson, N. O., Lorcerie, B., Guillevin, L., Mouthon, L., Saas, P., ... Bonnotte, B. (2012). Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis. Arthritis and Rheumatism, 64(11), 3788-3798. https://doi.org/10.1002/art.34647