Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Serbia.
J Neuroimmunol. 2013 Sep 15;262(1-2):72-8. doi: 10.1016/j.jneuroim.2013.07.001. Epub 2013 Jul 24.
Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1β, TNF, IFN-γ, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3+ T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NFκB signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis.
转铁蛋白（Tf）在 T 细胞激活和增殖中起主要作用。在这里，我们研究了 Tf 是否对 T 细胞具有免疫调节作用，以及在 T 细胞驱动的实验性自身免疫性脑脊髓炎（EAE）的发展中是否具有作用。虽然用脱铁转铁蛋白（ApoTf）处理刀豆蛋白 A 刺激的脾细胞不会影响白细胞介素 1β、肿瘤坏死因子、干扰素-γ、白细胞介素 17、白细胞介素 4 和白细胞介素 10 的释放，但它显著且剂量依赖性地下调了这些细胞中白细胞介素 2 的合成。ApoTf 还抑制了纯化的 CD3+T 细胞中白细胞介素 2 的生成，并且该作用伴随着丝裂原活化蛋白激酶 p44/42 和 NFκB 信号的下调。尽管白细胞介素 2的释放受到抑制，但 ApoTf 并没有抑制脾细胞的增殖。重要的是，ApoTf 改善了实验性自身免疫性脑脊髓炎模型小鼠的病情，并显著减少了蛋白脂质蛋白特异性淋巴细胞中白细胞介素 2 的体外产生。因此，ApoTf 可能是治疗多发性硬化症的一种有前途的有益药物。
