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NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica
  1. Christian Dejaco1,2,
  2. Christina Duftner1,3,
  3. Juman Al-Massad4,
  4. Annette D Wagner4,
  5. Joon-Keun Park4,
  6. Johannes Fessler2,
  7. Ariane Aigelsreiter5,
  8. Franz Hafner6,
  9. Sandra Vega7,
  10. William Sterlacci8,9,
  11. Beatrix Grubeck-Loebenstein7,
  12. Alexander Tzankov8,10,
  13. Thomas Ness11,
  14. Luigi Boiardi12,
  15. Carlo Salvarani12,
  16. Michael Schirmer1
  1. 1Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria
  2. 2Department of Rheumatology and Immunology, Medical University Graz, Graz, Austria
  3. 3Department of Internal Medicine, Hospital of Kufstein, Kufstein, Austria
  4. 4Department of Internal Medicine, Division of Nephrology, Hannover Medical School, Hannover, Germany
  5. 5Institute of Pathology, Medical University Graz, Graz, Austria
  6. 6Department of Angiology, Medical University Graz, Graz, Austria
  7. 7Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria
  8. 8Institute of Pathology, Innsbruck Medical University, Innsbruck, Austria
  9. 9Institute of Pathology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
  10. 10Institute of Pathology, University Hospital Basel, Basel, Switzerland
  11. 11University Clinic for Ophthalmology, Freiburg, Germany
  12. 12Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy
  1. Correspondence to Professor Michael Schirmer, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, Innsbruck A-6020, Austria; michael.schirmer{at}


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 NKG2D-ligands 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. NKG2D-ligands are present in temporal arteries and may co-stimulate NKG2D expressing T-cells.

  • Polymyalgia Rheumatica
  • Giant Cell Arteritis
  • T Cells

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