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粒细胞巨噬细胞集落刺激因子是一种针对胸腺树突状细胞的抗凋亡细胞因子,也是其辅助功能的重要调节因子。

Granulocyte-macrophage colony stimulating factor is an anti-apoptotic cytokine for thymic dendritic cells and a significant modulator of their accessory function.

作者信息

Vasilijić Sasa, Colić Miodrag, Vucević Dragana

机构信息

Institute of Medical Research, Military Medical Academy, Crnotravska 17, 11002 Belgrade, Yugoslavia.

出版信息

Immunol Lett. 2003 Mar 3;86(1):99-112. doi: 10.1016/s0165-2478(02)00295-x.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth-promoting factor for myeloid-derived dendritic cells (DC) but not for lymphoid DC. The data about its effect on thymic DC (TDC), which are both of lymphoid and myeloid origin, are very scarce. Using an in vitro model, we demonstrated in this work that GM-CSF significantly increased the survival of rat TDC in culture by inhibiting their apoptosis and the effect correlated with up-regulation of Bcl-2 expression. GM-CSF also stimulated differentiation and maturation of TDC as judged by higher expression of MHC class I and II molecules, CD54, CD80 and CD86. These changes correlated with stronger stimulatory activity of GM-CSF-pulsed TDC in syngeneic thymocyte proliferation assay and MLR. The stimulatory potential of TDC was further increased when thymocytes were cultivated with an anti-alphabeta TCR (R73) monoclonal antibody (mAb). The influence of unstimulated TDC on proliferation of thymocytes was inhibited by anti-CD86 but not anti-CD80 mAb, whereas in cultures with GM-CSF-treated TDC both mAbs exerted an additive blocking effect. After separation of TDC on CD11b(+) and CD11b(-) we demonstrated that GM-CSF inhibited apoptosis and potentiated accessory activity of both TDC subsets independently of the myeloid marker expression. Cummulatively, our results suggest that GM-CSF is one of the regulatory cytokine involved in survival, maturation, differentiation and accessory function of TDC.

摘要

粒细胞-巨噬细胞集落刺激因子(GM-CSF)是髓系来源的树突状细胞(DC)的生长促进因子,但不是淋巴样DC的生长促进因子。关于其对胸腺DC(TDC)(其兼具淋巴样和髓系起源)作用的数据非常稀少。在本研究中,我们使用体外模型证明,GM-CSF通过抑制大鼠TDC凋亡显著提高了其在培养中的存活率,且该作用与Bcl-2表达上调相关。GM-CSF还刺激了TDC的分化和成熟,这可通过MHC I类和II类分子、CD54、CD80和CD86的更高表达来判断。这些变化与GM-CSF刺激的TDC在同基因胸腺细胞增殖试验和混合淋巴细胞反应中的更强刺激活性相关。当胸腺细胞与抗αβTCR(R73)单克隆抗体(mAb)一起培养时,TDC的刺激潜能进一步增加。未刺激的TDC对胸腺细胞增殖的影响被抗CD86但不被抗CD80 mAb抑制,而在GM-CSF处理的TDC培养物中,两种mAb均发挥累加阻断作用。在根据CD11b(+)和CD11b(-)分离TDC后,我们证明GM-CSF抑制凋亡并增强两个TDC亚群的辅助活性,且与髓系标志物表达无关。总的来说,我们的结果表明GM-CSF是参与TDC存活、成熟、分化和辅助功能的调节性细胞因子之一。

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