title: NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica.
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 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.
authors: Department of Internal Medicine, Innsbruck Medical University, , Innsbruck, Austria.
authors: Christian
authors: C
authors: Dejaco
authors: Christina
authors: C
authors: Duftner
authors: Juman
authors: J
authors: Al-Massad
authors: Annette D
authors: AD
authors: Wagner
authors: Joon-Keun
authors: JK
authors: Park
authors: Johannes
authors: J
authors: Fessler
authors: Ariane
authors: A
authors: Aigelsreiter
authors: Franz
authors: F
authors: Hafner
authors: Sandra
authors: S
authors: Vega
authors: William
authors: W
authors: Sterlacci
authors: Beatrix
authors: B
authors: Grubeck-Loebenstein
authors: Alexander
authors: A
authors: Tzankov
authors: Thomas
authors: T
authors: Ness
authors: Luigi
authors: L
authors: Boiardi
authors: Carlo
authors: C
authors: Salvarani
authors: Michael
authors: M
authors: Schirmer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D016922:Cellular Senescence; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D013700:Giant Cell Arteritis / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D011111:Polymyalgia Rheumatica / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013699:Temporal Arteries / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D014409:Tumor Necrosis Factor-alpha; C423231:ULBP1 protein, human; C423230:ULBP2 protein, human; C423229:ULBP3 protein, human; D007371:Interferon-gamma
keywords: Giant Cell Arteritis; Polymyalgia Rheumatica; T Cells