Functional and T Cell Receptor Repertoire Analyses of Peripheral Blood and Infrapatellar Fat Pad T Cells in Knee Osteoarthritis.

Abstract

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). 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. 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. 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.