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.