Background: Pattern recognition receptors (PRRs) are receptors of the innate immune system which allow the recognition of bacteria, viruses, fungi and even host material. An unusual pro-inflammatory, cytotoxic T-cell subgroup lacking the co-stimulatory molecule CD28 has previously been described in immune mediated diseases different from giant cell arteritis/polymyalgia rheumatica (GCA/PMR). These T-cells need alternative pathways for activation and are therefore good candidates for the expression of PRRs.Methods: Surface expression of CD3, CD4, CD8, CD28, PRRs (CD14, TLR2 and TLR4) and intracellular staining for interferon γ (INF-γ) were performed using FACS analyses. Functional assays were performed with fresh PBMCs (>8 assays per experiment). As not normally distributed, data are shown as median±standard deviation and non-parametric tests were performed.Results: CD4+CD28null and CD8+CD28null T-cells are enriched in patients with GCA (4.5±8.5%, p<0.001 and 40.6±21.2%, p = 0.001) and pure PMR (2.1±7.4%, p<0.001 and 40.4±20.8%, p<0.001) compared to healthy controls (0.9±0.7% and 19.8±10.4%). Compared to their CD28+ counterpart CD4+CD28null T-cells express more CD14 (0.9±8.6%, p = 0.035), TLR4 (4.7±11.1%, p<0.001) and TLR2 (1.5±11.6%, p = 0.013) on their surface, whereas expression was negligible on CD4+CD28+ or CD8+ T-cells. Upon stimulation with lipopolysaccharide (LPS) CD4+CD28null T-cells produce INF-γ (5.9±6.5% in the presence of soluble CD14 versus 0.2±1.5, p = 0.007 as control without LPS). This IFN-γ production depends on CD14 (p = 0.047 between LPS stimulation with and without soluble CD14) and is independent from T-cell receptors (TCR).Conclusion: These results demonstrate an alternative mechanism of CD4+CD28null T-cells to produce IFN-γ in GCA/PMR by anomalous expressed PRRs independent of TCR.