Effects of activated T cells on osteoclastogenesis depend on how they are activated.
Effects of activated T cells on osteoclastogenesis depend on how they are activated.
复制标题
激活的 T 细胞对破骨细胞生成的影响取决于它们的激活方式。
DOI：
10.1016/j.bone.2004.04.022
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发表时间：
2004
期刊：
影响因子：
4.1
通讯作者：
Sylvester,FranciscoA
中科院分区：
文献类型：
--
作者：
Wyzga,Nancy;Varghese,Samuel;Wikel,Stephen;Canalis,Ernesto;Sylvester,FranciscoA
IntroductionActivated T cells are emerging as important regulators of osteoclast function in inflammatory diseases. Both pro- and anti-resorptive properties have been described. We reasoned that this reported variability of the effects of T cells on osteoclast formation depends on how T cells are activated in vitro.MethodsWe harvested T lymphocytes from 5-week-old C57BL/6 mouse spleens. Activation was performed with anti-CD3ε and -CD28 Ab (Abs), concanavalin A (Con A), phytohemagglutinin (PHA), or the superantigen Staphylococcal enterotoxin A (SEA). Osteoclastogenesis was induced by receptor activator of NF-κB ligand (RANKL) in the mouse macrophage cell line RAW 264.7 cells, or primary macrophage CD11b+cells from mouse spleen. Cells were cultured with T cells or with their conditioned medium.ResultsCo-culture of activated T lymphocytes with RAW 264.7 cells inhibited osteoclastogenesis but only when activated by Abs. This effect was CD4+-dependent. Conditioned medium from activated T lymphocytes with Abs consistently blocked osteoclastogenesis in RAW 264.7 and CD11b+cells. T cells activated with SEA, Con A, and PHA had inconsistent effects on osteoclastogenesis. We then tested the role of interferon (IFN)-γ, a known inhibitor of osteoclastogenesis, in the effects of T cells on osteoclast formation. IFN-γ neutralizing antibody blocked the inhibitory effect of T-cell conditioned medium on osteoclastogenesis. Osteoclast precursors from IFN-γ receptor-null mice treated with 0.1% medium from activated T cells formed osteoclasts. However, higher doses of medium inhibited osteoclastogenesis, so that we cannot exclude that other factors besides IFN-γ may be involved.ConclusionsAvailable methods to activate T lymphocytes result in variable effects on osteoclastogenesis. IFN-γ is the main factor responsible for the inhibitory effects of activated T cells on osteoclast formation.
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