CD4+CD25+Foxp3+ T cells and CD4+CD'25-Foxp3+ T cells in aged mice
CD4+CD25+Foxp3+ T cells and CD4+CD'25-Foxp3+ T cells in aged mice
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DOI：
10.4049/jimmunol.176.11.6586
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Sakaguchi, Shimon
中科院分区：
文献类型：
--
作者：
Nishioka, Tomohisa;Shimizu, Jun;Sakaguchi, Shimon
衰老与T细胞介导的免疫应答的进行性下降有关。然而，尚不清楚调节性/抑制性CD 4 T细胞是否参与这种下降。我们的体外分析显示，老年小鼠中的CD 4（+）CD 25（+）T细胞，即充分表征的天然存在的调节性/抑制性CD 4 T细胞，在功能上与年轻小鼠中的那些相当（即，无反应性和抑制性），尽管数量略有增加。相反，在老年小鼠中，整个CD 4（+）CD 25（-）T细胞的功能变化是明显的，即，大部分老化的CD 4（+）CD 25（-）T细胞表现出明显的低反应性，其余细胞保持正常的反应性。此外，我们在老化的低反应性CD 4（+）CD 25（-）T细胞中鉴定了Foxp 3（一种赋予CD 4 T细胞调节/抑制功能的关键转录因子）阳性的抑制性CD 4 T细胞。这些结果表明，T细胞介导的免疫应答的年龄相关性下降可归因于CD 4（+）CD 25（-）T细胞群的变化，而不是抑制性CD 4（+）CD 25（+）T细胞的功能增强。
Aging is associated with a progressive decline in T cell-mediated immune responses. However, it has been unknown whether regulatory/suppressive CD4 T cells are involved in this decline. Our in vitro analyses revealed that CD4(+) CD25(+) T cells, the well-characterized naturally occurring regulatory/suppressive CD4 T cells, in aged mice are functionally comparable to those in young mice (i.e., anergic and suppressive), although slightly increased in number. In contrast, functional changes to whole CD4(+)CD25(-) T cells were pronounced in aged mice, i.e., the majority of aged CD4(+)CD25(-) T cells exhibited a significant hyporesponsiveness, and the remaining cells maintained a normal responsiveness. Furthermore, we identified Foxp3 (a transcription factor critical in conferring the regulatory/suppressive function to CD4 T cells)-positive suppressive CD4 T cells among aged hyporesponsive CD4(+)CD25(-) T cells. These results suggest that the age-related decline in T cell-mediated immune responses is ascribable to changes in the CD4(+)CD25(-) T cell population and not to a functional augmentation of suppressive CD4(+)CD25(+) T cells.