The pathogenesis of osteolysis in failed total hip arthroplasty is not fully understood. The purpose of this study is to identify CD4+CD25+ Regulatory T cells in periprosthetic tissues in failed total hip replacements secondary to osteolysis. Intra-operative tissue samples and peripheral blood were collected from patients undergoing revision total hip arthroplasty surgery. Regulatory T cells were present in the tissues, and significantly increased in the peripheral blood in patients with failed total hips compared to normal controls. Further characterization of these regulatory T cells are warranted as they may play a role in osteolysis in loose total hip replacements. Osteolysis remains the most common complication following total joint arthroplasty. To date, no authors have investigated the role of CD4+CD25+ regulatory T cells (TREG) participating in the osteolytic pathogenesis. The purpose of this study is to quantitate the presence of TREG cells in periprosthetic tissues in failed total hip replacements secondary to osteolysis. Fifteen consecutive patients booked for revision total hip arthroplasty secondary to osteolysis were included. Tissue samples were collected: peripheral blood (PB), synovial fluid (SF), synovial tissue (ST), and interface tissue (IT) between the failed component and the bone defect. Total lymphocytes were isolated and analyzed using fluorescent-tagged antibody cell sorting (FACS) for the presence of TREG cells. Frozen sections of ST and IT were analyzed with immunohistochemistry for TREG cells. TREG cells were significantly upregulated (p<
0.01) in the PB (68%) of revision hip patients compared to normal controls PB (44%). In the synovial tissue (ST) and interface tissue (IT), 57% of the lymphocytes isolated were TREG cells. The presence of TREG cells in the ST and IT were confirmed with immunohistochemistry. TREG cells are upregulated in the peripheral blood of patients with failed total hips secondary to osteolysis. The TREG cells are also present in the synovial tissue and interface tissue. Evidence for involvement of regulatory T cells contribute to our understanding of this complex biologic response to artificial wear particles. Functional studies of these TREG cells are warranted as they are upregulated in patients with loose total hip replacements.