Diminished primary CD8 T cell response to viral infection during protein energy malnutrition in mice is due to changes in microenvironment and low numbers of viral-specific CD8 T cell precursors
Diminished primary CD8 T cell response to viral infection during protein energy malnutrition in mice is due to changes in microenvironment and low numbers of viral-specific CD8 T cell precursors
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DOI：
10.1093/jn/138.4.806
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发表时间：
2008-04-01
影响因子：
4.2
通讯作者：
Kapasi, Zoher E.
中科院分区：
文献类型：
--
作者：
Chatraw, Janel Hart;Wherry, E. John;Kapasi, Zoher E.
蛋白质能量营养不良（PEM）增加了感染的发生率和严重程度，导致营养不良人群的发病率和死亡率。病毒特异性细胞是保护性免疫的重要组成部分。我们假设病毒特异性细胞的扩增和PEM宿主的微环境的减少导致感染的发生率和严重程度增加。我们使用淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染的小鼠模型和使用携带对D-b限制性LCMV糖蛋白33-41表位具有特异性的T细胞受体的P14转基因小鼠细胞的过继转移系统来验证这一假设。我们将相同数量的P14细胞从喂食足够的18%蛋白质或低0.6%蛋白质饮食的小鼠转移到喂食足够蛋白质（AP）或低蛋白质（LP）饮食2周的C57 BL/6小鼠中，用LCMV感染它们，并在感染后1周随访。在PEM期间，原代病毒特异性CD 8 T细胞的扩增减少;在LP饮食喂养的小鼠中，其仅为AP饮食喂养的小鼠中的2-3%。此外，PEM期间减少的原发性CD 8 T细胞应答可能部分是由于病毒特异性CD 8 T细胞数量少和微环境改变。
Protein energy malnutrition (PEM) increases the incidence and severity of infection, causing morbidity and mortality in malnourished populations. Viral-specific cells are an important component of protective immunity. We hypothesized that reduction in the expansion of viral-specific cells and the microenvironment of the PEM host leads to increased incidence and severity of infections. We tested this hypothesis using a mouse model of lymphocytic choriomeningitis virus (LCMV) infection and an adoptive transfer system using P14 transgenic mice cells bearing T cell receptors specific for the D-b-restricted LCMV glycoprotein 33-41 epitope. We transferred equal numbers of P14 cells from mice fed either an adequate, 18% protein or low, 0.6% protein diet into C57BL/6 mice that had been fed adequate-protein (AP) or low-protein (LP) diets for 2 wk, infected them with LCMV, and followed them 1 wk postinfection. During PEM, the expansion of primary viral-specific CD8 T cells diminished; in LP diet-fed mice, it was only 2-3% of that in the AP diet-fed mice. Furthermore, the diminished primary CD8 T cell response during PEM may in part have been due to low numbers of viral-specific CD8 T cells and an altered microenvironment.