Characterization of t cell secreted cytokines and cytotoxic mediators profiling in knee osteoarthritis patients

Abstract

Osteoarthritis (OA) is a chronic disease associated with morphological joint changes that results in the breakdown of joint cartilage and underlying bone with erosive inflammation. Factors of OA are intrinsic factor and extrinsic factor. The pathogenesis of OA relates with immune responses and immune cells, T cells, B cells, and macrophages etc., T cells both CD4+ and CD8+ T cell are immune cells that have been suggested to play a role in OA. However, we found many finding in CD8+ T cells such as a high proportion of CD8+ T cell was observed in tissue of knee joint. In addition, a trend for higher frequency for CD8+ T cell with older in OA patients. In our study, we collected peripheral blood and infrapatellar fat pad (IFPs) from knee OA patients and measured their cytokine/cytotoxic granule production and the frequency of degranulating (CD107a+) from both CD4+ and CD8+ T cells. We determined the relation between, their cytokine (IL-1b, IL-17, IL-6, TNF and IFN-g), cytotoxic granules (perforin, granzymeB, granulysin) production and degranulating cells of CD4+ and CD8+ T cells with Kellgren-Lawrence (KL) radiographic gradings. We found that TNF-producing CD8+ T cells from peripheral blood of OA patients was a higher level than healthy individual. IL-1b, IL-6 and TNF-producing both CD4+ and CD8+ T cell were increased in IFP of knee OA patients. In addition, the presence of degranulating cell-producing CD8+ T cell both in peripheral blood and IFP from knee OA patients revealed a higher level than healthy individuals. Moreover, our data showed perforin/granulysin in CD4+ T cells and perforin/granzyme B in CD8+ T cell were a higher level in IFP of knee OA patients when compared to peripheral blood of knee OA patients. We observed no correlation between cytokines/cytotoxic granules and CD107a, with grade 3, grade 4. We were also detectable and a high level to IL-6, sFas, granzyme A, perforin and granulysin in synovial fluid of OA patients. This study provides a more understanding about the mechanism of knee OA pathogenesis and lead to the development of drug design for OA treatment and to find soluble factors as a prognostic marker for knee OA.