Osteoclastogenesis in peripheral blood mononuclear cell cultures of periprosthetic osteolysis patients and the phenotype of T cells localized in periprosthetic tissues

Arthroplasty is a very successful medical procedure. Failures depend on aseptic loosening caused by periprosthetic osteolysis, where Tcells have a contradictory role.We analyzed osteoclastogenesis in peripheral blood mononuclear cell (PBMC) cultures of periprosthetic osteolysis patients and the phenotype of T cells localized in periprosthetic tissues. We enrolled 45 subjects with periprosthetic osteolysis (15), stable prosthesis (15) and healthy controls (15). We performed PBMC cultures to study osteoclastogenesis. Osteoclasts and Tcell phenotypewere examined byimmunohistochemistry,immunofluorescence and flow citometry. Periprosthetic osteolysis patients showed spontaneous osteoclastogenesis, whichwas inhibited by RANK-Fc and T cell depletion. In periprosthetic osteolysis patients’ PBMC cultures, CD4 and CD8 T cells increased and CD8 T cells did not express CD25. In periprosthetic tissues T cells were close to osteoclasts, suggesting their interaction. Local CD8 Tcells showed a regulatory phenotype, expressing CD25 and FoxP3, while CD4 T cells did not express activation markers. Our data suggest that, in an early stage of periprosthetic osteolysis, T cells may promote osteoclastogenesis, whereas subsequently osteoclasts activate FoxP3/CD8 T cells, which inhibit CD4 effector T cells. This mechanism may explain the previous finding of non-active T cells in periprosthetic tissues.