Activated T lymphocytes support osteoclast formation in vitro

Activated T lymphocytes support osteoclast formation in vitro
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DOI:
10.1006/bbrc.1999.1623
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发表时间:
1999-11-11
影响因子:
3.1
通讯作者:
Gillespie, MT
Gillespie, MT
中科院分区:
生物学4区
文献类型:
--
作者:
Horwood, NJ;Kartsogiannis, V;Gillespie, MT

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成骨基质细胞能够在成骨因子如1 α,25(OH)(2)D-3, PTH和IL-11存在的情况下支持造血前体形成破骨细胞,成骨基质细胞产生nf - κ B配体受体激活剂(RANKL), TNF配体家族的II型膜蛋白,以响应这些药物。活化的T淋巴细胞也产生RANKL;然而,这种细胞类型在体外支持破骨细胞形成的能力尚不清楚。用α - cd3包被磁珠提取的人pbmc来源的T细胞,在Con A和一组细胞因子存在下与粘附的小鼠脾细胞共培养。在Con A存在下,体外激活T细胞形成真正的破骨细胞,IL-1 α和TGF β进一步增强破骨细胞数量。与诱导破骨细胞形成的药物相同,pmc来源的淋巴细胞在24小时内显示RANKL mRNA表达增加。在RA患者淋巴样浸润的滑膜组织切片中,CD3(+) T细胞表达RANKL。激活的T淋巴细胞支持破骨细胞形成的能力可能为类风湿关节炎等疾病状态下增强破骨细胞形成和骨吸收提供了一种机制。(C) 1999学术出版社。
Osteoblastic stromal cells are capable of supporting osteoclast formation from 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 receptor activator of NF-kappa B 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 alpha CD3-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-1 alpha and TGF beta 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. (C) 1999 Academic Press.