Protracted course of lymphocytic choriomeningitis virus WE infection in early life:: Induction but limited expansion of CD8+ effector T cells and absence of memory CD8+ T cells
Protracted course of lymphocytic choriomeningitis virus WE infection in early life:: Induction but limited expansion of CD8+ effector T cells and absence of memory CD8+ T cells
复制标题
DOI：
10.1128/jvi.00062-07
复制
发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Siegrist, Claire-Anne
中科院分区：
文献类型：
--
作者：
Belnoue, Elodie;Fontannaz-Bozzotti, Paola;Siegrist, Claire-Anne
人类婴儿的病毒感染通常遵循一个漫长的过程，与年龄较大的儿童的病毒感染相比，病毒载量更高，病毒清除延迟。为了确定这种长期感染模式的机制，我们在2周大的BALB/c小鼠中使用具有良好特征的淋巴细胞性脉络丛脑膜炎病毒（LCMV） we株建立了婴儿感染小鼠模型。成年小鼠在感染后8天就能清除病毒，而幼鼠的LCMV滴度在感染后持续数周。lcmv特异性效应CD8+ T细胞在幼龄小鼠中被诱导，并在第7天完全发挥功能，但从第12天开始迅速消退，无法恢复。我们在这里表明，这是由于lcmv特异性CD8+ T细胞扩增失败和缺乏保护性lcmv特异性记忆CD8+ T细胞造成的。在这些早期生活条件下，病毒控制和清除最终只能通过lcmv特异性B细胞来实现，这些B细胞有助于保护幼鼠免于早期死亡或慢性感染。
Viral infections in human infants frequently follow a protracted course, with higher viral loads and delayed viral clearance compared to viral infections in older children. To identify the mechanisms responsible for this protracted pattern of infection, we developed an infant infection murine model using the well-characterized lymphocytic choriomeningitis virus (LCMV) WE strain in 2-week-old BALB/c mice. In contrast to adult mice, in which viral clearance occurred as expected 8 days after infection, LCMV titers persisted for several weeks after infection of infant mice. LCMV-specific effector CD8+ T cells were elicited in infant mice and fully functional on day 7 but rapidly waned and could not be recovered from day 12 onwards. We show here that this results from the failure of LCMV-specific CD8+ T cells to expand and the absence of protective LCMV-specific memory CD8+ T cells. Under these early life conditions, viral control and clearance are eventually achieved only through LCMV-specific B cells that contribute to protect infant mice from early death or chronic infection.