Jiang Jiu, Gross Diara, Nogusa Shoko, Elbaum Philip, Murasko Donna M
Department of Microbiology and Immunology, Drexel University, Philadelphia, PA 19129, USA.
J Immunol. 2005 Aug 1;175(3):1820-6. doi: 10.4049/jimmunol.175.3.1820.
Type I IFN (IFN-I or IFN-alphabeta) plays an important role in the innate immune response against viral infection. Here we report that a potent inducer of IFN-alphabeta, 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-alphabeta Ab. Although poly(I:C) stimulated lower circulating levels of IFN-alphabeta in aged mice, administration of IFN-alphabeta after poly(I:C) did not induce depletion of T cells in aged mice. These results indicate that IFN-alphabeta plays a critical role in the depletion of T cells of young mice, and further suggest that the lower level of functional IFN-alphabeta 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.
I型干扰素（IFN-I或IFN-αβ）在针对病毒感染的先天性免疫反应中发挥重要作用。在此我们报告，一种强效的IFN-αβ诱导剂，聚肌苷酸-聚胞苷酸[poly(I:C)]，导致年轻小鼠而非老年小鼠的T细胞耗竭，并且这种耗竭仅限于中枢记忆T细胞而非效应记忆T细胞。尽管通过CD69证明，poly(I:C)在体内对T细胞的早期激活不受衰老影响，但与老年小鼠相比，年轻小鼠中活性半胱天冬酶-3的表达更高。poly(I:C)对年轻小鼠T细胞的这种耗竭以及对年轻和老年小鼠中活性半胱天冬酶-3的诱导以及CD69的诱导均被抗IFN-αβ抗体阻断。尽管poly(I:C)在老年小鼠中刺激产生的循环IFN-αβ水平较低，但在poly(I:C)后给予IFN-αβ并未诱导老年小鼠的T细胞耗竭。这些结果表明，IFN-αβ在年轻小鼠T细胞的耗竭中起关键作用，并且进一步表明，老年小鼠在poly(I:C)后功能性IFN-αβ水平较低以及T细胞中活性半胱天冬酶-3的诱导减少可能是老年小鼠T细胞对耗竭的抵抗力增加的原因。
