Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ.
University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, Tucson, AZ.
J Immunol. 2024 Oct 1;213(7):965-970. doi: 10.4049/jimmunol.2400113.
CMV drives the accumulation of virus-specific, highly differentiated CD8 memory T cells (memory inflation [MI]). In mice, MI was shown to directly correlate with the CMV infection dose, yet the CMV-associated CD8 MI plateaus over time. It is unclear how MI is regulated with aging. We infected young mice with 102, 104, and 106 PFU of murine CMV and confirmed that MI magnitude was directly proportional to the infectious dose, reaching a setpoint by midlife. By old age, MI subsided, most prominently in mice infected with 106 PFU, and reached statistical parity between groups in 26-mo-old mice. This corresponded to an age-related loss in lymphatic endothelial cells in lymph nodes, recently shown to be sufficient to drive MI in mice. We propose that MI size and persistence over the lifespan is controlled by the size of the lymphatic endothelial cell niche, whose shrinking leads to reduced MI with aging.
CMV 驱动病毒特异性、高度分化的 CD8 记忆 T 细胞（记忆膨胀 [MI]）的积累。在小鼠中，已经证明 MI 与 CMV 感染剂量直接相关，但随着时间的推移，CMV 相关的 CD8 MI 趋于平稳。目前尚不清楚 MI 如何随着衰老而调节。我们用 102、104 和 106 PFU 的鼠 CMV 感染年轻小鼠，并证实 MI 幅度与感染剂量成正比，在中年达到一个设定值。到老年时，MI 消退，尤其是在感染 106 PFU 的小鼠中，并且在 26 月龄的小鼠中，各组之间达到统计学上的平衡。这与最近在小鼠中显示足以驱动 MI 的淋巴结淋巴管内皮细胞的年龄相关丢失相对应。我们提出，MI 的大小和在整个生命周期中的持久性受淋巴管内皮细胞生态位的大小控制，随着年龄的增长，其缩小导致 MI 减少。
