Counting antigen-specific CD8 T cells: A reevaluation of bystander activation during viral infection

Counting antigen-specific CD8 T cells: A reevaluation of bystander activation during viral infection
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DOI:
10.1016/s1074-7613(00)80470-7
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发表时间:
1998-02-01
期刊:
影响因子:
32.4
通讯作者:
Ahmed, R
Ahmed, R
中科院分区:
医学1区
文献类型:
--
作者:
Murali-Krishna, K;Altman, JD;Ahmed, R

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病毒感染在体内诱导广泛的T细胞增殖,但大多数应答T细胞的特异性尚未确定。为了解决这个问题,我们使用了含有病毒肽的MHC I类分子的四聚体,以在小鼠的急性LCMV感染期间直接可视化抗原特异性CD 8 T细胞。基于四聚体结合和两种在单细胞水平上测量干扰素-γ产生的灵敏测定,我们发现50%-70%的活化的CD 8 T细胞是LCMV特异性的(2 × 107个病毒特异性细胞/脾)。病毒清除后,抗原特异性CD 8 T细胞数量下降至每个脾脏10(6)个,并在小鼠的一生中维持在该水平。在用LCMV再激发后,记忆T细胞迅速扩增,但在用异源牛痘病毒感染后,LCMV特异性记忆CTL的数量没有可检测到的变化。因此,在病毒感染过程中观察到的大部分CD 8 T细胞扩增代表抗原特异性细胞,并保证了我们目前对抗病毒反应大小的想法的修订。
Viral infections induce extensive T cell proliferation in vivo, but the specificity of the majority of the responding T cells has not been defined. To address this issue we used tetramers of MHC class I molecules containing viral peptides to directly visualize antigen-specific CD8 T cells during acute LCMV infection of mice. Based on tetramer binding and two sensitive assays measuring interferon-gamma production at the single-cell level, we found that 50%-70% of the activated CD8 T cells were LCMV specific (2 x 10(7) virus-specific cells/spleen). Following viral clearance, antigen-specific CD8 T cell numbers dropped to 10(6) per spleen and were maintained at this level for the life of the mouse. Upon rechallenge with LCMV, there was rapid expansion of memory T cells, but after infection with the heterologous vaccinia virus there was no detectable change in the numbers of LCMV-specific memory CTL. Therefore, much of the CD8 T cell expansion seen during viral infection represents antigen-specific cells and warrants a revision of our current thinking on the size of the antiviral response.