Age-associated decrease in virus-specific CD8+T lymphocytes during primary influenza infection
Age-associated decrease in virus-specific CD8+T lymphocytes during primary influenza infection
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DOI：
10.1016/s0047-6374(02)00010-6
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发表时间：
2002-04-30
影响因子：
5.3
通讯作者：
Murasko, DM
中科院分区：
文献类型：
--
作者：
Po, JLZ;Gardner, EM;Murasko, DM
在原发性肺部甲型流感病毒感染期间，在年轻成年（6个月）和老年（22个月）C57 BL/6小鼠中检查了小鼠对病毒感染的CD 8 + T细胞应答的年龄相关性降低的机制。在肺淋巴细胞中观察到与年龄相关的CD 8 + T细胞结合含有甲型流感病毒核蛋白（NP）表位的MHC I类四聚体的百分比（P < 0.0001）和数量（P <0.05）以及病毒特异性CTL活性（P <0.05）的显著降低。单个小鼠的NP + CD 8+细胞百分比与NP特异性细胞毒活性（r（2）= 0.77，P < 0.02）和产生干扰素-γ的CD 8+细胞百分比（r（2）= 0.86，P < 0.002）在年轻和老年小鼠中均强烈相关。在来自两个年龄组的小鼠的NP + CD 8+淋巴细胞上检测到相当的CD 28、CD 25和记忆CD 44（hi）/CD 62 L（lo）表型表达。与年轻小鼠相比，老年小鼠NP + CD 8+细胞的最大扩增延迟，这导致最大细胞毒活性和病毒清除延迟。这些数据表明，在原发性甲型流感感染期间，年龄相关的CD 8+淋巴细胞活性受损是由于流感特异性CD 8 + T细胞的扩增缺陷，而不是效应活性缺陷。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
The mechanism of the age-associated decrease in CD8 + T cell response of mice to virus infection was examined in young adult (6 months) and aged (22 months) C57BL/6 mice during primary pulmonary influenza A virus infection. A significant age-associated decrease in both the percentage (P < 0.0001) and number (P < 0.05) of CD8 + T cells binding MHC Class I tetramers containing influenza A nucleoprotein (NP) epitope and in virus-specific CTL activity (P < 0.05) was observed with pulmonary lymphocytes. The percentage of NP + CD8 + cells of individual mice strongly correlated with NP-specific cytotoxic activity (r(2) = 0.77, P < 0.02) and with the percentage of CD8 + cells that produced interferon-gamma (r(2) = 0.86, P < 0.002) in both young and aged mice. Comparable expression of the CD28, CD25, and the memory CD44(hi)/CD62L(lo) phenotype was detected on NP + CD8 + lymphocytes from mice of both age groups. There was a delay in the maximal expansion of NP + CD8 + cells in aged compared to young mice that paralleled a delay in maximal cytotoxic activity and in virus clearance. These data suggest that the age-related impairment of CD8 + lymphocyte activity during a primary influenza A infection is due to a defect in the expansion, rather than in effector activity, of influenza-specific CD8 + T cells. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.