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 journalArticle

20 Citations (Scopus)

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

Fingerprint

Polymyalgia Rheumatica
Giant Cell Arteritis
T-cells
T-Lymphocytes
Temporal Arteries
Adventitia
Vasa Vasorum
Tissue
Ligands
Interleukin-15
Flow cytometry
Fluorescent Antibody Technique
Ligation
Assays
Flow Cytometry

ASJC Scopus subject areas

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

Cite this

Dejaco, C., Duftner, C., Al-Massad, J., Wagner, A. D., Park, J. K., Fessler, J., ... Schirmer, M. (2013). NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica. Annals of the Rheumatic Diseases, 72(11), 1852-1859. https://doi.org/10.1136/annrheumdis-2012-201660

NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica. / Dejaco, Christian; Duftner, Christina; Al-Massad, Juman; Wagner, Annette D.; Park, Joon Keun; Fessler, Johannes; Aigelsreiter, Ariane; Hafner, Franz; Vega, Sandra; Sterlacci, William; Grubeck-Loebenstein, Beatrix; Tzankov, Alexander; Ness, Thomas; Boiardi, Luigi; Salvarani, Carlo; Schirmer, Michael.

In: Annals of the Rheumatic Diseases, Vol. 72, No. 11, 11.2013, p. 1852-1859.

Research output: Contribution to journalArticle

Dejaco, C, Duftner, C, Al-Massad, J, Wagner, AD, Park, JK, Fessler, J, Aigelsreiter, A, Hafner, F, Vega, S, Sterlacci, W, Grubeck-Loebenstein, B, Tzankov, A, Ness, T, Boiardi, L, Salvarani, C & Schirmer, M 2013, 'NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica', Annals of the Rheumatic Diseases, vol. 72, no. 11, pp. 1852-1859. https://doi.org/10.1136/annrheumdis-2012-201660
Dejaco, Christian ; Duftner, Christina ; Al-Massad, Juman ; Wagner, Annette D. ; Park, Joon Keun ; Fessler, Johannes ; Aigelsreiter, Ariane ; Hafner, Franz ; Vega, Sandra ; Sterlacci, William ; Grubeck-Loebenstein, Beatrix ; Tzankov, Alexander ; Ness, Thomas ; Boiardi, Luigi ; Salvarani, Carlo ; Schirmer, Michael. / NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica. In: Annals of the Rheumatic Diseases. 2013 ; Vol. 72, No. 11. pp. 1852-1859.
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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.",
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AU - Dejaco, Christian

AU - Duftner, Christina

AU - Al-Massad, Juman

AU - Wagner, Annette D.

AU - Park, Joon Keun

AU - Fessler, Johannes

AU - Aigelsreiter, Ariane

AU - Hafner, Franz

AU - Vega, Sandra

AU - Sterlacci, William

AU - Grubeck-Loebenstein, Beatrix

AU - Tzankov, Alexander

AU - Ness, Thomas

AU - Boiardi, Luigi

AU - Salvarani, Carlo

AU - Schirmer, Michael

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N2 - 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.

AB - 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.

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