Age-associated decline in effective immune synapse formation of CD4+ T cells is reversed by vitamin E supplementation
Age-associated decline in effective immune synapse formation of CD4+ T cells is reversed by vitamin E supplementation
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DOI：
10.4049/jimmunol.178.3.1443
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Meydani, Simin Nikbin
中科院分区：
文献类型：
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作者：
Marko, Melissa G.;Ahmed, Tanvir;Meydani, Simin Nikbin
衰老与 IL-2 产生和 T 细胞增殖减少有关。在老年动物和人类中，补充维生素 E 可以增加幼稚 T 细胞的细胞分裂和 IL-2 的产生。免疫突触在 T 细胞和 APC 之间的接触部位形成并参与 T 细胞激活。我们评估了维生素 E 是否影响信号蛋白向免疫突触的重新分配。来自年轻和年老小鼠脾脏的纯化 CD4(+) T 细胞用维生素 E 处理，然后用表达抗 CD3 的替代 APC 进行刺激。使用共聚焦荧光显微镜，我们观察到，与年轻小鼠的细胞相比，年老小鼠的 CD4(+) T 细胞向免疫突触募集信号蛋白的可能性明显较低。维生素 E 增加了能够形成有效免疫突触的旧 CD4 T 细胞的百分比。在体内补充维生素 E 后也发现了类似的结果。与记忆细胞相比，来自老年小鼠的幼稚 T 细胞在免疫突触形成方面更有缺陷，并且对维生素 E 补充更敏感。这些数据首次表明，维生素 E 显着改善了幼稚 CD4(+) T 细胞中与年龄相关的早期 T 细胞信号传导事件。
Aging is associated with reduced IL-2 production and T cell proliferation. Vitamin E supplementation, in aged animals and humans, increases cell division and IL-2 production by naive T cells. The immune synapse forms at the site of contact between a T cell and an APC and participates in T cell activation. We evaluated whether vitamin E affects the redistribution of signaling proteins to the immune synapse. Purified CD4(+) T cells, from the spleens of young and old mice, were treated with vitamin E before stimulation with a surrogate APC expressing anti-CD3. Using confocal fluorescent microscopy, we observed that CD4(+) T cells from old mice were significantly less likely to recruit signaling proteins to the immune synapse than cells from young mice. Vitamin E increased the percentage of old CD4 T cells capable of forming an effective immune synapse. Similar results were found following in vivo supplementation with vitamin E. When compared with memory cells, naive T cells from aged mice were more defective in immune synapse formation and were more responsive to vitamin E supplementation. These data show, for the first time, that vitamin E significantly improves age-related early T cell signaling events in naive CD4(+) T cells.