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 (T_REG) participating in the osteolytic pathogenesis. The purpose of this study is to quantitate the presence of T_REG 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 T_REG cells. Frozen sections of ST and IT were analyzed with immunohistochemistry for T_REG cells.

T_REG 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 T_REG cells in the ST and IT were confirmed with immunohistochemistry.

T_REG 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 T_REG cells are warranted as they are upregulated in patients with loose total hip replacements.

T cells have been implicated in the pathogenesis of osteolysis. The goal of this study was to compare the ratios of CD4+ T cell populations in total hip arthroplasty (THA) patients with and without osteolysis. We found no significant differences in the frequency of peripheral blood CD4+CD25+ regulatory and effector T cells, serum IL-10 and TGF-β concentrations, and immuno-suppressive ability of regulatory T cells from patients with osteoarthritis prior to THA, and THA patients with and without radiographic evidence of osteolysis.

CD4+ T cells are critical in regulating immune-mediated conditions. This study compared the frequency of CD4+ T cell subpopulations in the peripheral blood of patients with and without osteolysis following total hip arthroplasty (THA).

Numbers of CD4+CD25hi regulatory T cells, CD4+CD25moderate effector T cells, and CD4+CD25+ T cells in the peripheral blood of thirty patients with osteoarthritis prior to primary THA, thirty patients with asymptomatic THAs and no radiographic evidence of osteolysis, nineteen patients with asymptomatic THAs with radiographic evidence of early osteolysis (not requiring revision surgery) and nine patients scheduled for revision THA for osteolysis were determined by flow cytometry. Serum IL-10 and TGF-β levels were measured using ELISA kits. Results were compared by t-test and rank sum test. CD4+ CD25hi regulatory T cells and CD4+ CD25neg T cells were isolated from blood using a MACS cell isolation kit, co-cultured for three days, and T cell proliferation determined by [3H]-thy-midine uptake.

The frequency of CD4+CD25hi regulatory T cells, CD4+CD25moderate effector T cells, and CD4+CD25+ T cells were similar in each study group. Regulatory T cells from patients with and without osteolysis had a normal functional ability to inhibit CD4+ T cell proliferation. Serum levels of the regulatory T cell-derived cytokines IL-10 and TGF-β were also comparable between groups.

Our data suggests that CD4+ T cell immune responses are normal in THA regardless of the level of osteolysis, in contrast to previous studies that have implicated T cell hypersensitivity in the pathogenesis of osteolysis surrounding THA.