A diverse repertoire of naïve T cells is thought to be essential for a robust response to new infections. However, a key aspect of aging of the T cell compartment is a decline in numbers and diversity of peripheral naïve T cells. We have hypothesized that the age-related decline in naïve T cells forces the immune system to respond to new infections using cross-reactive memory T cells generated to previous infections that dominate the aged peripheral T cell repertoire. Here we confirm that the CD8 T cell response of aged, influenza-naïve mice to primary infection with influenza virus is dominated by T cells that derive from the memory T cell pool. These cells exhibit the phenotypic characteristics of virtual memory cells rather than true memory cells. Furthermore, we find that the repertoire of responding CD8 T cells is constrained compared with that of young mice, and differs significantly between individual aged mice. After infection, these virtual memory CD8 T cells effectively develop into granzyme-producing effector cells, and clear virus with kinetics comparable to naïve CD8 T cells from young mice. The response of aged, influenza-naive mice to a new influenza infection is mediated largely by memory CD8 T cells. However, unexpectedly, they have the phenotype of VM cells. In response to de novo influenza virus infection, the VM cells develop into granzyme-producing effector cells and clear virus with comparable kinetics to young CD8 T cells.

中文翻译：

---

虚拟记忆细胞对未患流感的老年小鼠对流感病毒感染的反应做出了重大贡献

人们认为，多样化的初始 T 细胞库对于对新感染做出强有力的反应至关重要。然而，T 细胞室老化的一个关键方面是外周幼稚 T 细胞数量和多样性的下降。我们假设幼稚 T 细胞与年龄相关的下降迫使免疫系统使用交叉反应性记忆 T 细胞对新感染做出反应，这些 T 细胞对以前的感染产生了主导老年外周 T 细胞库的感染。在这里，我们确认老年、未感染流感的小鼠对流感病毒初次感染的 CD8 T 细胞反应主要由源自记忆 T 细胞池的 T 细胞控制。这些细胞表现出虚拟记忆细胞的表型特征，而不是真正的记忆细胞。此外，我们发现，与年轻小鼠相比，响应 CD8 T 细胞的所有组成部分受到限制，并且在个体老年小鼠之间存在显着差异。感染后，这些虚拟记忆 CD8 T 细胞有效地发育成产生颗粒酶的效应细胞，并清除病毒，其动力学可与年轻小鼠的幼稚 CD8 T 细胞相媲美。未患流感的老年小鼠对新的流感感染的反应主要由记忆 CD8 T 细胞介导。然而，出乎意料的是，它们具有 VM 细胞的表型。为响应从头流感病毒感染，VM 细胞发育成产生颗粒酶的效应细胞并清除具有与年轻 CD8 T 细胞相当的动力学的病毒。这些虚拟记忆 CD8 T 细胞有效地发育成产生颗粒酶的效应细胞，并清除病毒，其动力学可与来自年轻小鼠的幼稚 CD8 T 细胞相媲美。未患流感的老年小鼠对新的流感感染的反应主要由记忆 CD8 T 细胞介导。然而，出乎意料的是，它们具有 VM 细胞的表型。为响应从头流感病毒感染，VM 细胞发育成产生颗粒酶的效应细胞并清除具有与年轻 CD8 T 细胞相当的动力学的病毒。这些虚拟记忆 CD8 T 细胞有效地发育成产生颗粒酶的效应细胞，并清除病毒，其动力学可与来自年轻小鼠的幼稚 CD8 T 细胞相媲美。未患流感的老年小鼠对新的流感感染的反应主要由记忆 CD8 T 细胞介导。然而，出乎意料的是，它们具有 VM 细胞的表型。为响应从头流感病毒感染，VM 细胞发育成产生颗粒酶的效应细胞并清除具有与年轻 CD8 T 细胞相当的动力学的病毒。