TY - JOUR
T1 - Activated T lymphocytes support osteoclast formation in vitro
AU - Horwood, Nicole J.
AU - Kartsogiannis, Vicky
AU - Quinn, Julian M.W.
AU - Romas, Evangelos
AU - Martin, T. John
AU - Gillespie, Matthew T.
PY - 1999/11/11
Y1 - 1999/11/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033547343&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1999.1623
DO - 10.1006/bbrc.1999.1623
M3 - Article
C2 - 10548505
AN - SCOPUS:0033547343
VL - 265
SP - 144
EP - 150
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -