NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica

Christian Dejaco, Christina Duftner, Juman Al-Massad, Annette D. Wagner, Joon Keun Park, Johannes Fessler, Ariane Aigelsreiter, Franz Hafner, Sandra Vega, William Sterlacci, Beatrix Grubeck-Loebenstein, Alexander Tzankov, Thomas Ness, Luigi Boiardi, Carlo Salvarani, Michael Schirmer

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To investigate functional expression of NKG2D on CD4 and CD8 T-cells in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). Methods: Peripheral blood was drawn from patients with GCA (n=16), PMR (n=78) and healthy controls (HC, n=64). Tissue samples were obtained from GCA patients and controls. Proliferation and cytokine production assays were performed using CFSE and intracellular IFN-γ or TNF-α staining, respectively, and flow cytometry analysis. Immunofluorescence and immunohistology were applied to analyse the presence of NKG2D- expressing T-cells and NKG2D-ligands in temporal arteries, respectively. mRNA levels of NKG2Dligands were determined by RT-PCR. Results: In both GCA and PMR patients, NKG2D was preferentially expressed on senescent CD4CD28- and CD8CD28-, as well as on CD8CD28 T-cells. Frequencies of senescent T-cells were increased in GCA and PMR patients compared to HC. In GCA tissue samples, infiltrating T-cells were predominately CD28-. NKG2D expressing T-cells concentrated around the vasa vasorum of the adventitia. Antigenic stimulation induced rapid up-regulation of NKG2D on CD4CD28- and CD4CD28 T-cells, whereas TNF-α and interleukin-15 enhanced NKG2D expression on senescent CD4 and CD8 T-cells only. NKG2D cross-linkage augmented anti-CD3 triggered proliferation, IFN-γ and TNF-α production of CD8 T-cells. In CD4CD28- T-cells, NKG2D ligation resulted in increased IFN-γ production only. NKG2D ligands were expressed in temporal arteries from GCA patients, particularly in the adventitial and medial layers of affected vessels. Conclusions: NKG2D is functionally expressed on CD4CD28- and CD8 T-cells in GCA and PMR. NKG 2Dligands are present in temporal arteries and may co-stimulate NKG2D expressing T-cells.

Original languageEnglish
Pages (from-to)1852-1859
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume72
Issue number11
DOIs
Publication statusPublished - Nov 2013

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy
  • Medicine(all)

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