Objective.Osteoarthritis (OA) is a condition that features inflammation and immune responses of innate and adaptive immunity. The role of T cells in knee OA pathogenesis is still unclear. Our aim was to characterize T cell functions and their clonality in patients with knee OA in peripheral blood (PB) and infrapatellar fat pads (IPFP).Methods.We isolated T cells from PB and IPFP of patients with knee OA and PB of healthy individuals and determined soluble mediators produced from these cells. In addition, we performed a clonal analysis of activated CD8+ T cells and compared the T cell receptor β-variable gene chain (TRBV) usages between T cells in PB and IPFP of patients with knee OA.Results.Our results suggest that in patients with knee OA, circulating T cells possess a more “cytotoxic” profile or rather impaired cytokine production, but the knee microenvironment allows for these T cells to produce proinflammatory cytokines [interleukin (IL)-1β, IL-6, tumor necrosis factor], IL-17, and interferon-γ within IPFP. Activated CD8+ IPFP T cells carry different repertoire distribution from those present in PB of patients with knee OA. Shared TRBV usage of activated CD8+ IPFP T cells among the 3 patients with knee OA was also observed.Conclusion.Our study describes the nature of T cells in knee OA that may be due to “unhealthy” aging or other factors that drive healthy aging T cells into a state of imbalance, thus contributing to the pathogenesis of knee OA.
Objective
The purpose of this study was to investigate the effects of osteoarthritis (OA) peripheral blood mononuclear cell (PBMC) ‐stimulating proteoglycan aggrecan peptides on T cells present in infrapatellar fat pads (IPFPs) and synovial tissues, and to correlate these findings with mediators present in synovial fluid of OA patients.
Methods
We tested for interleukin‐6 (IL‐6) ‐producing T cells in IPFPs of patients with knee OA using ELISPOT. Cytokine and cytotoxic mediator production from OA PBMCs, IPFPs, synovial tissues, and synovial fluids in response to proteoglycan aggrecan peptides were quantified by cytometric bead array. Patterns of cytokine and cytotoxic mediator production were analyzed and compared.
Results
T cells from IPFPs elicited strong responses towards the p263‐280 peptide by secreting IL‐6. In addition, there was a trend that the p263‐280 peptide stimulated higher production of cytokines/cytotoxic mediators than other proteoglycan aggrecan peptides, although this was not statistically significant. In patients with knee OA, a group of cytotoxic mediators (sFas, perforin, granzyme A, and granulysin) and IL‐6 were detectable at high levels from the synovial fluid. In addition, inflammation in patients with knee OA was more pronounced in joint‐surrounding tissues than levels in circulating peripheral blood.
Conclusion
Our data suggest that T cells responding to the p263‐280 peptide contribute to the secretion of various soluble mediators that are found within the synovial fluid. We also identified potential new candidates that may serve as biomarkers of knee OA.
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