Activated T lymphocytes support osteoclast formation in vitro

Nicole J. Horwood, Vicky Kartsogiannis, Julian M. W. Quinn, Evangelos Romas, T. John Martin, Matthew T. Gillespie

Research output: Contribution to journalArticlepeer-review

359 Citations (Scopus)

Abstract

Osteoblastic stromal cells are capable of supporting osteoclast formation from hematopoietic precursors in the presence of osteotropic factors such as 1alpha,25(OH)(2)D(3), PTH, and IL-11. Osteoblastic stromal cells produce receptor activator of NF-kappaB ligand (RANKL), a type II membrane protein of the TNF ligand family, in response to these agents. Activated T lymphocytes also produce RANKL; however, the ability of this cell type to support osteoclast formation in vitro is unknown. Human PBMC-derived T cells, extracted using alphaCD3-coated magnetic beads, were cocultured with adherent murine spleen cells in the presence of Con A and a panel of cytokines. In the presence of Con A, bona fide osteoclasts were formed in vitro with activated T cells: IL-1alpha and TGFbeta further enhanced osteoclast numbers. PBMC-derived lymphocytes showed an increase in the mRNA expression of RANKL within 24 h of treatment with the same agents that were used to induce osteoclast formation. In synovial tissue sections with lymphoid infiltrates from RA patients, the expression of RANKL was demonstrated in CD3(+) T cells. The ability of activated T lymphocytes to support osteoclast formation may provide a mechanism for the potentiation of osteoclast formation and bone resorption in disease states such as rheumatoid arthritis.

Original languageEnglish
Pages (from-to)144-150
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume265
Issue number1
DOIs
Publication statusPublished - 11 Nov 1999

Keywords

  • Aged
  • Animals
  • Animals, Newborn
  • Arthritis, Rheumatoid/immunology
  • Carrier Proteins/biosynthesis
  • Cell Differentiation
  • Coculture Techniques
  • Concanavalin A/pharmacology
  • Female
  • Gene Expression Regulation
  • Hematopoietic Stem Cells/cytology
  • Humans
  • Interleukin-2/pharmacology
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins/biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Osteoclasts/cytology
  • RANK Ligand
  • RNA, Messenger/genetics
  • Receptor Activator of Nuclear Factor-kappa B
  • Stromal Cells/cytology
  • Synovial Membrane/immunology
  • T-Lymphocytes/immunology
  • Transcription, Genetic/drug effects
  • Transforming Growth Factor beta/pharmacology

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