Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux.
Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux.
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DOI：
10.1016/j.celrep.2016.11.037
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发表时间：
2016-12-13
期刊：
影响因子：
8.8
通讯作者：
Ladell K
中科院分区：
文献类型：
--
作者：
Ahmed R;Roger L;Costa Del Amo P;Miners KL;Jones RE;Boelen L;Fali T;Elemans M;Zhang Y;Appay V;Baird DM;Asquith B;Price DA;Macallan DC;Ladell K
适应性免疫需要从胸腺中选择的原始前体产生记忆T细胞。这个过程中的关键中介是干细胞样记忆T细胞（TSCM），这是一种多能祖细胞，可以自我更新和补充更多分化的记忆T细胞亚群。理论上，TSCM库中的抗原特异性可能作为休眠细胞的一种功能而被静态地印记，或者被更短暂的亚群动态地保留。为了探索免疫记忆的起源，我们使用重水稳定同位素标记法测量了TSCM细胞在体内的周转。这些数据表明，青年和老年受试者的TSCM细胞都是通过持续的增殖来维持的。与这一发现一致，TSCM细胞表现出有限的端粒长度侵蚀，并伴有高水平的活性端粒酶和Ki67的表达。总的来说，这些观察结果表明，TSCM细胞在人类的整个生命周期中处于一种不断变化的状态。人类干细胞样记忆T细胞（TSCM）在体内广泛增殖，人类TSCM细胞高水平表达Ki67，人类TSCM细胞端粒长，人类TSCM细胞表现出高水平的端粒酶活性，干细胞样记忆T细胞（TSCM）是多功能祖细胞，可以自我更新和补充更多分化的记忆T细胞亚群。Ahmed等人发现，人类TSCM细胞通过持续增殖得以维持，端粒长度有限侵蚀，同时端粒活性酶和Ki67的表达水平较高。
Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (TSCM) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the TSCM pool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of TSCM cells in vivo using stable isotope labeling with heavy water. The data indicate that TSCM cells in both young and elderly subjects are maintained by ongoing proliferation. In line with this finding, TSCM cells displayed limited telomere length erosion coupled with high expression levels of active telomerase and Ki67. Collectively, these observations show that TSCM cells exist in a state of perpetual flux throughout the human lifespan. Human stem cell-like memory T (TSCM) cells proliferate extensively in vivo Human TSCM cells express high levels of Ki67 Human TSCM cells have long telomeres Human TSCM cells display high levels of telomerase activity Stem cell-like memory T (TSCM) cells are multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. Ahmed et al. find that human TSCM cells are maintained by ongoing proliferation and display limited telomere length erosion coupled with high expression levels of active telomerase and Ki67.
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影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
影响因子：
2.9
作者：
Neese, RA;Siler, SQ;Hellerstein, MK
通讯作者：
Hellerstein, MK
影响因子：
82.9
作者：
Hellerstein, M;Hanley, MB;McCune, JM
通讯作者：
McCune, JM
DOI：
10.1073/pnas.232551499
发表时间：
2002-11-26
影响因子：
11.1
作者：
Neese, RA;Misell, LM;Hellerstein, MK
通讯作者：
Hellerstein, MK
影响因子：
15.9
作者：
McCune, JM;Hanley, MB;Hellerstein, M
通讯作者：
Hellerstein, M