Differential expansion of T central memory precursor and effector subsets is regulated by division speed
Differential expansion of T central memory precursor and effector subsets is regulated by division speed
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DOI：
10.1038/s41467-019-13788-w
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发表时间：
2020-01-08
影响因子：
16.6
通讯作者：
Buchholz, Veit R.
中科院分区：
文献类型：
--
作者：
Kretschmer, Lorenz;Flossdorf, Michael;Buchholz, Veit R.
虽然抗原致敏的T细胞以接近哺乳动物细胞生理最大值的速度增殖，但在缺乏抗原的情况下，T细胞记忆通过罕见的细胞分裂得以维持。这些不同的增殖程序之间的过渡一直难以通过基于人群的分析来解决。在这里，我们计算重建单个CD 8（+）T细胞在接种疫苗后的增殖历史，并测量体内新兴T细胞亚群的分裂速度。我们发现，较慢的循环中央记忆的前体，其特征是一个延长的G1期，分离早期从大部分快速分裂的效应子亚群，并进一步减缓其细胞周期后过早去除抗原刺激。相反，炎症刺激的可用性减少选择性地抑制效应T细胞增殖，这是由于对白细胞介素-2的接受性降低。与这些发现一致，在整个克隆扩增过程中，抗原性而非炎症性刺激的持续性决定了记忆区室的后期大小。
While antigen-primed T cells proliferate at speeds close to the physiologic maximum of mammalian cells, T cell memory is maintained in the absence of antigen by rare cell divisions. The transition between these distinct proliferative programs has been difficult to resolve via population-based analyses. Here, we computationally reconstruct the proliferative history of single CD8(+) T cells upon vaccination and measure the division speed of emerging T cell subsets in vivo. We find that slower cycling central memory precursors, characterized by an elongated G1 phase, segregate early from the bulk of rapidly dividing effector subsets, and further slow-down their cell cycle upon premature removal of antigenic stimuli. In contrast, curtailed availability of inflammatory stimuli selectively restrains effector T cell proliferation due to reduced receptivity for interleukin-2. In line with these findings, persistence of antigenic but not inflammatory stimuli throughout clonal expansion critically determines the later size of the memory compartment.