Depletion of T cells by type I interferon: Differences between young and aged mice
Depletion of T cells by type I interferon: Differences between young and aged mice
复制标题
DOI：
10.4049/jimmunol.175.3.1820
复制
发表时间：
2005-08-01
影响因子：
4.4
通讯作者：
Murasko, DM
中科院分区：
文献类型：
--
作者：
Jiang, J;Gross, D;Murasko, DM
I型干扰素(干扰素-I或干扰素-α-β)在抵抗病毒感染的先天免疫反应中发挥着重要作用。在这里，我们报告了一种有效的干扰素-α-β诱导剂，多聚肌苷-多胞苷[聚(I：C)]，导致年轻但不是老年小鼠的T细胞耗尽，这种耗竭仅限于中央记忆，而不是效应记忆，T细胞。虽然CD69显示，聚(I：C)在体内对T细胞的早期激活并没有随着年龄的增长而减弱，但年轻小鼠的活性caspase-3的表达比老年小鼠高。抗干扰素-α-β抗体可阻断聚(I：C)对幼龄小鼠T细胞的这种耗竭和对caspase-3活性的诱导，以及对幼年和老年小鼠CD69的诱导。尽管聚(I：C)刺激老龄小鼠循环中较低水平的干扰素-α-β，但在聚(I：C)之后给予干扰素-α-β不会导致老龄小鼠T细胞的耗竭。这些结果表明，干扰素-αβ在幼年小鼠T细胞耗竭中起重要作用，进一步提示聚(I：C)后衰老小鼠T细胞功能性干扰素-α水平降低和caspase-3活性诱导减少可能是老龄小鼠T细胞对耗竭抵抗力增强的原因之一。
Type I IFN (IFN-I or IFN-alpha beta) plays an important role in the innate immune response against viral infection. Here we report that a potent inducer of IFN-alpha beta, polyinosinic-polycytidylic acid [poly(I:C)], led to the depletion of T cells in young, but not aged mice, and that this depletion was limited to central memory, but not effector memory, T cells. Although early activation of T cells in vivo by poly(I:C), as demonstrated by CD69, was not impaired with aging, the expression of active caspase-3 was higher in young compared with aged mice. This depletion of T cells and induction of active caspase-3 in young mice and of CD69 in both young and aged mice by poly(I:C) were blocked by anti-IFN-alpha beta Ab. Although poly(I:C) stimulated lower circulating levels of IFN-alpha beta in aged mice, administration of IFN-alpha beta after poly(I:C) did not induce depletion of T cells in aged mice. These results indicate that IFN-alpha beta plays a critical role in the depletion of T cells of young mice, and further suggest that the lower level of functional IFN-alpha beta and decreased induction of active caspase-3 in T cells of aged mice after poly(I:C) may be responsible for the increased resistance of T cells of aged mice to depletion.