title: Osteoclastogenesis in peripheral blood mononuclear cell cultures of periprosthetic osteolysis patients and the phenotype of T cells localized in periprosthetic tissues.
abstract: Arthroplasty is a very successful medical procedure. Failures depend on aseptic loosening caused by periprosthetic osteolysis, where T cells 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 T cell phenotype were examined by immunohistochemistry, immunofluorescence and flow citometry. Periprosthetic osteolysis patients showed spontaneous osteoclastogenesis, which was 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 T cells 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.
authors.affiliation: CeRMS (Center for Research and Medical Studies), A.O.U. San Giovanni Battista, Turin, Italy. roato78@libero.it
authors.forename: Ilaria
authors.initials: I
authors.lastname: Roato
authors.forename: Davide
authors.initials: D
authors.lastname: Caldo
authors.forename: Lucia
authors.initials: L
authors.lastname: D'Amico
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Amelio
authors.forename: Laura
authors.initials: L
authors.lastname: Godio
authors.forename: Salvatore
authors.initials: S
authors.lastname: Patanè
authors.forename: Franco
authors.initials: F
authors.lastname: Astore
authors.forename: Guido
authors.initials: G
authors.lastname: Grappiolo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Boggio
authors.forename: Roberto
authors.initials: R
authors.lastname: Scagnelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Molfetta
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ferracini
mesh_terms: D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D010014:Osteolysis / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit