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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.
AuthorsIlaria Roato, Davide Caldo, Lucia D'Amico, Patrizia D'Amelio, Laura Godio, Salvatore Patanè, Franco Astore, Guido Grappiolo, Maurizio Boggio, Roberto Scagnelli, Luigi Molfetta, Riccardo Ferracini
JournalBiomaterials (Biomaterials) Vol. 31 Issue 29 Pg. 7519-25 (Oct 2010) ISSN: 1878-5905 [Electronic] Netherlands
PMID20638717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Interleukin-2 Receptor alpha Subunit
Topics
  • Arthroplasty, Replacement, Hip (adverse effects)
  • CD4-Positive T-Lymphocytes (metabolism)
  • CD8-Positive T-Lymphocytes (metabolism)
  • Cells, Cultured
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Interleukin-2 Receptor alpha Subunit (metabolism)
  • Leukocytes, Mononuclear (metabolism, pathology)
  • Osteoclasts (metabolism, pathology)
  • Osteolysis (etiology, immunology, metabolism, pathology)
  • T-Lymphocytes

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