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. conclusions: 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.