In vivo dynamics of anti-viral CD8 T cell responses to different epitopes. An evaluation of bystander activation in primary and secondary responses to viral infection.

In vivo dynamics of anti-viral CD8 T cell responses to different epitopes. An evaluation of bystander activation in primary and secondary responses to viral infection.
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抗病毒 CD8 T 细胞对不同表位反应的体内动态。

DOI:
10.1007/978-1-4615-5355-7_14
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发表时间:
1998
影响因子:
--
通讯作者:
Ahmed,R
Ahmed,R
中科院分区:
医学4区
文献类型:
--
作者:
Murali-Krishna,K;Altman,JD;Suresh,M;Sourdive,D;Zajac,A;Ahmed,R

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病毒感染可诱导体内大量T细胞增殖,但只有一小部分(1-5%)的活化T细胞是病毒特异性的,这就导致人们普遍认为大多数T细胞的增殖是病毒介导的旁观者活化和/或非特异性细胞的交叉反应性刺激。为了重新检查这个问题,我们使用三种敏感技术在小鼠的急性LCMV感染期间定量抗原特异性CD 8 T细胞:(i)细胞内细胞因子产生,(ii)单细胞ELISPOT和(iii)通过用MHC I类四聚体+肽染色直接可视化抗原特异性CD 8 T细胞。与先前的估计相反,我们发现50-70%的活化的CD 8 T细胞是LCMV特异性的。这表示在8天内增加≥ 10,000倍(约2 × 107个病毒特异性细胞/脾),在第3天和第5天之间出现扩增峰值,在此期间,病毒特异性CD 8 T细胞的估计分裂时间约为8小时。病毒清除后,抗原特异性CD 8 T细胞的数量降至1 × 106/脾,并在小鼠的一生中维持在该水平。在用LCMV再激发后,记忆性CD 8 T细胞迅速增殖并再次占总CD 8 T细胞的>50%。相反,在用异源病毒如牛痘攻击时,LCMV特异性记忆CTL的数量没有变化,尽管活化的CD 8 T细胞的数量显著增加。总之,这些结果表明,在病毒感染期间观察到的大部分CD 8 T细胞扩增代表抗原特异性细胞。
Viral infections induce extensive T cell proliferationin vivo.However, only a small fraction (1–5%) of the activated T cells have been shown to be virus specific leading to the prevailing notion that most of the T cell expansion represents cytokine-mediated bystander activation and/or cross reactive stimulation of non specific cells. To re-examine this issue we quantitated antigen specific CD8 T cells during acute LCMV infection of mice using three sensitive techniques: (i) intracellular cytokine production, (ii) single cell ELISPOT and (iii) direct visualization of antigen specific CD8 T cells by staining with MHC class I tetramers + peptide. In contrast to previous estimates, we found that 50–70% of the activated CD8 T cells were LCMV specific. This represented ≥ 10,000-fold increase (~2 × 107virus specific cells/spleen) in 8 days with the peak expansion occurring between day 3 and 5 during which period virus specific CD8 T cells had an estimated division time of ~8 hours. Following viral clearance, the number of antigen specific CD8 T cells dropped to 1 × 106per spleen and were maintained at this level for the life of the mouse. Upon rechallenge with LCMV, memory CD8 T cells rapidly proliferated and again comprised >50% of the total CD8 T cells. In contrast, upon challenge with a heterologous virus such as vaccinia, there was no change in the number of LCMV specific memory CTL, despite a substantial increase in the number of activated CD8 T cells. Taken together, these results show that much of the CD8 T cell expansion seen during viral infection represents antigen specific cells.
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