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

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346 Citations (Scopus)

Abstract

Osteoblastic stromal cells are capable of supporting osteoclast formation from hematopoietic precursors in the presence of osteotropic factors such as 1α,25(OH)2D3, PTH, and IL-11. Osteoblastic stromal cells produce receptor activator of NF-κB 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 αCD3-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-1α and TGFβ 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
Externally publishedYes

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