Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness.
Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness.
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DOI：
10.1371/journal.pbio.2005523
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发表时间：
2018-06
期刊：
影响因子：
9.8
通讯作者：
Asquith B
中科院分区：
文献类型：
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作者：
Costa Del Amo P;Lahoz-Beneytez J;Boelen L;Ahmed R;Miners KL;Zhang Y;Roger L;Jones RE;Marraco SAF;Speiser DE;Baird DM;Price DA;Ladell K;Macallan D;Asquith B
适应性免疫依赖于记忆T细胞的产生和维持，以提供针对重复抗原暴露的保护。据推测，一个自我更新的T细胞群，称为干细胞样记忆T（TSCM）细胞，负责维持记忆。然而，目前尚不清楚TSCM细胞在体内的动力学是否与这一假设相一致。为了解决这个问题，我们研究了TSCM细胞在人体内生理条件下的动力学，采用多学科方法，结合数学建模，稳定同位素标记，端粒长度分析和疫苗接种者的横截面数据。我们发现，出乎意料的是，TSCM克隆的平均寿命非常短（半衰期< 1年，自我更新的程度= 430天）：太短，无法构成干细胞群。然而，我们也发现，TSCM人口是由至少2个动力学不同的亚群，以不同的速度翻。虽然一个亚群被快速替换（半衰期= 5个月）并解释了大量TSCM群体的快速平均转换，但另一个TSCM亚群的半衰期约为9年，与回忆应答的寿命一致。我们还表明，后者群体表现出高度的自我更新，细胞在我们一生中的15%时间内不会死亡或分化。最后，虽然人口不多，但并不受过度随机性的影响。我们的结论是，大多数的TSCM细胞不是干细胞样的，但有一个亚群的TSCM细胞的动力学是兼容的，其假定的作用，在维持T细胞的记忆。人体免疫系统会记住以前遇到的病原体，因此，在第二次遇到相同的病原体时，反应会更快，更有效。这种免疫记忆是所有疫苗接种的基础。免疫记忆可以持续几十年，但记忆是如何维持的还不清楚。据推测，有一个专门的细胞群称为干细胞样记忆T（TSCM）细胞，具有干细胞样行为，并负责T细胞记忆的持久性。在这里，我们表明，一个子集的TSCM细胞，在健康的人体内，具有动态的自我更新和克隆寿命所需的维持长寿的免疫记忆。
Adaptive immunity relies on the generation and maintenance of memory T cells to provide protection against repeated antigen exposure. It has been hypothesised that a self-renewing population of T cells, named stem cell–like memory T (TSCM) cells, are responsible for maintaining memory. However, it is not clear if the dynamics of TSCM cells in vivo are compatible with this hypothesis. To address this issue, we investigated the dynamics of TSCM cells under physiological conditions in humans in vivo using a multidisciplinary approach that combines mathematical modelling, stable isotope labelling, telomere length analysis, and cross-sectional data from vaccine recipients. We show that, unexpectedly, the average longevity of a TSCM clone is very short (half-life < 1 year, degree of self-renewal = 430 days): far too short to constitute a stem cell population. However, we also find that the TSCM population is comprised of at least 2 kinetically distinct subpopulations that turn over at different rates. Whilst one subpopulation is rapidly replaced (half-life = 5 months) and explains the rapid average turnover of the bulk TSCM population, the half-life of the other TSCM subpopulation is approximately 9 years, consistent with the longevity of the recall response. We also show that this latter population exhibited a high degree of self-renewal, with a cell residing without dying or differentiating for 15% of our lifetime. Finally, although small, the population was not subject to excessive stochasticity. We conclude that the majority of TSCM cells are not stem cell–like but that there is a subpopulation of TSCM cells whose dynamics are compatible with their putative role in the maintenance of T cell memory. The human immune system remembers previously encountered pathogens so that, on meeting the same pathogen a second time, the response is quicker and more effective. This immune memory is the basis of all vaccinations. Immune memory persists for decades, but how memory is maintained is unclear. It has been hypothesised that there is a dedicated population of cells called stem cell–like memory T (TSCM) cells that have stem cell–like behaviour and are responsible for the persistence of T cell memory. Here, we show that a subset of TSCM cells, in healthy humans in vivo, have the dynamic properties of self-renewal and clonal longevity necessary to maintain long-lived immune memory.
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影响因子：
4.3
作者：
Ganusov VV;Borghans JA;De Boer RJ
通讯作者：
De Boer RJ
影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C
影响因子：
64.8
作者：
Busch, Katrin;Klapproth, Kay;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
4.4
作者：
Crotty, S;Felgner, P;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1038/nri3567
发表时间：
2014-01
期刊：
Nature reviews. Immunology
影响因子：
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