Activated T lymphocytes support osteoclast formation in vitro

Osteoblastic stromal cells are capable of supporting osteoclast formation f rom hematopoietic precursors in the presence of osteotropic factors such as 1 alpha,25(OH)(2)D-3, PTH, and IL-11, Osteoblastic stromal cells produce r eceptor activator of NF-kappa B ligand (RANKL), a type II membrane protein of the TNF ligand family, in response to these agents. Activated T lymphocy tes also produce RANKL; however, the ability of this cell type to support o steoclast formation in vitro is unknown. Human PBMC-derived T cells, extrac ted using alpha CD3-coated magnetic beads, were cocultured with adherent mu rine 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 activat ed T cells: IL-1 alpha and TGF beta further enhanced osteoclast numbers. PB MC-derived lymphocytes showed an increase in the mRNA expression of RANKL w ithin 24 h of treatment with the same agents that were used to induce osteo clast formation. In synovial tissue sections with lymphoid infiltrates from RA patients, the expression of RANKL was demonstrated in CD3(+) T cells. T he ability of activated T lymphocytes to support osteoclast formation may p rovide a mechanism for the potentiation of osteoclast formation and bone re sorption in disease states such as rheumatoid arthritis. (C) 1999 Academic Press.