1. NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica
- Author
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Thomas Ness, Christian Dejaco, Franz Hafner, Sandra C Vega, Johannes Fessler, Juman Al-Massad, Michael Schirmer, Ariane Aigelsreiter, Carlo Salvarani, Beatrix Grubeck-Loebenstein, Joon Keun Park, Alexander Tzankov, Christina Duftner, William Sterlacci, Luigi Boiardi, and Annette D. Wagner
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Pathology ,medicine.medical_treatment ,Autoimmunity ,CD8-Positive T-Lymphocytes ,80 and over ,Immunology and Allergy ,Giant Cell Arteritis ,Polymyalgia Rheumatica ,T Cells ,Aged ,Aged, 80 and over ,Case-Control Studies ,Cell Aging ,Female ,GPI-Linked Proteins ,Histocompatibility Antigens Class I ,Humans ,Intercellular Signaling Peptides and Proteins ,Interferon-gamma ,Intracellular Signaling Peptides and Proteins ,Middle Aged ,NK Cell Lectin-Like Receptor Subfamily K ,Real-Time Polymerase Chain Reaction ,Signal Transduction ,Temporal Arteries ,Tumor Necrosis Factor-alpha ,Up-Regulation ,Cellular Senescence ,medicine.diagnostic_test ,CD28 ,Cytokine ,medicine.anatomical_structure ,medicine.medical_specialty ,T cell ,Immunology ,Biology ,Immunofluorescence ,General Biochemistry, Genetics and Molecular Biology ,Flow cytometry ,Rheumatology ,medicine ,NKG2D ,medicine.disease ,Molecular biology ,Giant cell arteritis ,CD8 - Abstract
Objective To investigate functional expression of NKG 2 D 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 NKG 2 D-expressing T-cells and NKG 2 D-ligands in temporal arteries, respectively. mRNA levels of NKG 2 D-ligands were determined by RT-PCR. Results In both GCA and PMR patients, NKG 2 D 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 − . NKG 2 D expressing T-cells concentrated around the vasa vasorum of the adventitia. Antigenic stimulation induced rapid up-regulation of NKG 2 D on CD4CD28 − and CD4CD28 T-cells, whereas TNF-α and interleukin-15 enhanced NKG 2 D expression on senescent CD4 and CD8 T-cells only. NKG 2 D cross-linkage augmented anti-CD3 triggered proliferation, IFN-γ and TNF-α production of CD8 T-cells. In CD4CD28 − T-cells, NKG 2 D ligation resulted in increased IFN-γ production only. NKG 2 D ligands were expressed in temporal arteries from GCA patients, particularly in the adventitial and medial layers of affected vessels. Conclusions NKG 2 D is functionally expressed on CD4CD28 − and CD8 T-cells in GCA and PMR. NKG 2 D-ligands are present in temporal arteries and may co-stimulate NKG 2 D expressing T-cells.
- Published
- 2013