Meryk Andreas, Grasse Marco, Balasco Luigi, Kapferer Werner, Grubeck-Loebenstein Beatrix, Pangrazzi Luca
Immunology group, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria.
Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Antioxidants (Basel). 2020 Nov 19;9(11):1152. doi: 10.3390/antiox9111152.
Aging is characterized by reduced immune responses, a process known as immunosenescence. Shortly after their generation, antigen-experienced adaptive immune cells, such as CD8 and CD4 T cells, migrate into the bone marrow (BM), in which they can be maintained for long periods of time within survival niches. Interestingly, we recently observed how oxidative stress may negatively support the maintenance of immunological memory in the BM in old age. To assess whether the generation and maintenance of immunological memory could be improved by scavenging oxygen radicals, we vaccinated 18-months (old) and 3-weeks (young) mice with alum-OVA, in the presence/absence of antioxidants vitamin C (Vc) and/or N-acetylcysteine (NAC). To monitor the phenotype of the immune cell population, blood was withdrawn at several time-points, and BM and spleen were harvested 91 days after the first alum-OVA dose. Only in old mice, memory T cell commitment was boosted with some antioxidant treatments. In addition, oxidative stress and the expression of pro-inflammatory molecules decreased in old mice. Finally, changes in the phenotype of dendritic cells, important regulators of T cell activation, were additionally observed. Taken together, our data show that the generation and maintenance of memory T cells in old age may be improved by targeting oxidative stress.
衰老的特征是免疫反应减弱,这一过程被称为免疫衰老。抗原接触过的适应性免疫细胞,如CD8和CD4 T细胞,在产生后不久就迁移到骨髓(BM)中,在那里它们可以在生存龛中长时间维持。有趣的是,我们最近观察到氧化应激可能对老年骨髓中免疫记忆的维持产生负面影响。为了评估清除氧自由基是否可以改善免疫记忆的产生和维持,我们在有/无抗氧化剂维生素C(Vc)和/或N-乙酰半胱氨酸(NAC)的情况下,用明矾-卵清蛋白(alum-OVA)对18个月大(老年)和3周大(幼年)的小鼠进行免疫接种。为了监测免疫细胞群体的表型,在几个时间点采集血液,并在首次注射明矾-卵清蛋白后91天收获骨髓和脾脏。仅在老年小鼠中,一些抗氧化剂处理增强了记忆T细胞的形成。此外,老年小鼠的氧化应激和促炎分子的表达降低。最后,还观察到树突状细胞(T细胞激活的重要调节因子)表型的变化。综上所述,我们的数据表明,针对氧化应激可能改善老年记忆T细胞的产生和维持。