Activated T lymphocytes support osteoclast formation in vitro.
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.
Horwood
N J
NJ
St. Vincent's Institute of Medical Research and University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, 3065, Australia.
Kartsogiannis
V
V
Quinn
J M
JM
Romas
E
E
Martin
T J
TJ
Gillespie
M T
MT
D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D017154:Stromal Cells / Q000166:cytology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002352:Carrier Proteins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D003208:Concanavalin A