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Activated T Lymphocytes Support Osteoclast Formation in Vitro

1999; Elsevier BV; Volume: 265; Issue: 1 Linguagem: Inglês

10.1006/bbrc.1999.1623

1090-2104

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

Bone health and treatments

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.