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 language | English |
|---|---|
| Pages (from-to) | 1852-1859 |
| Number of pages | 8 |
| Journal | Annals of the Rheumatic Diseases |
| Volume | 72 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2013 |
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ASJC Scopus subject areas
- Rheumatology
- Immunology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Allergy
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica
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
PY - 2013/11
Y1 - 2013/11
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.
UR - http://www.scopus.com/inward/record.url?scp=84885167306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885167306&partnerID=8YFLogxK
U2 - 10.1136/annrheumdis-2012-201660
DO - 10.1136/annrheumdis-2012-201660
M3 - Article
C2 - 23417963
AN - SCOPUS:84885167306
VL - 72
SP - 1852
EP - 1859
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 11
ER -