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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.
NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica.
Ann Rheum Dis. 2013; 72(11):1852-1859
Doi: 10.1136/annrheumdis-2012-201660
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
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Dejaco Christian
- Co-Autor*innen der Med Uni Graz
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Aigelsreiter Ariane
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Fessler Johannes
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Hafner Franz
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- Abstract:
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To investigate functional expression of NKG2D on CD4 and CD8 T-cells in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
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.
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.
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.
- Find related publications in this database (using NLM MeSH Indexing)
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Aged -
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Aged, 80 and over -
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Autoimmunity -
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CD4-Positive T-Lymphocytes - metabolism
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CD8-Positive T-Lymphocytes - metabolism
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Case-Control Studies -
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Cell Aging -
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Female -
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GPI-Linked Proteins - genetics
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Giant Cell Arteritis - metabolism
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Histocompatibility Antigens Class I - genetics
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Humans -
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Intercellular Signaling Peptides and Proteins - genetics
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Interferon-gamma - metabolism
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Intracellular Signaling Peptides and Proteins - genetics
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Male -
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Middle Aged -
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NK Cell Lectin-Like Receptor Subfamily K - metabolism
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Polymyalgia Rheumatica - metabolism
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Real-Time Polymerase Chain Reaction -
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Signal Transduction -
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Temporal Arteries - metabolism
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Tumor Necrosis Factor-alpha - metabolism
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Up-Regulation -
- Find related publications in this database (Keywords)
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Polymyalgia Rheumatica
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Giant Cell Arteritis
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T Cells