CD57(+) Memory T Cells Proliferate In Vivo.
CD57(+) Memory T Cells Proliferate In Vivo.
复制标题
DOI：
10.1016/j.celrep.2020.108501
复制
发表时间：
2020-12-15
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;Miners KL;Lahoz-Beneytez J;Jones RE;Roger L;Baboonian C;Zhang Y;Wang ECY;Hellerstein MK;McCune JM;Baird DM;Price DA;Macallan DC;Asquith B;Ladell K
淋巴细胞生物学领域的一个中心范式认为，复制性衰老记忆T细胞表达碳水化合物表位CD 57。然而，这些细胞随着年龄的增长而积累，并在持续的抗原刺激下在数量上扩增。在这里，我们使用体内氘标记和离体分析端粒长度，端粒酶活性和细胞周期标志物Ki 67的细胞内表达来区分两种非排他性的情况：（1）CD 57+记忆T细胞不增殖，而是通过从CD 57 −记忆T细胞库的表型转变而产生;和/或（2）CD 57+记忆T细胞通过隔室内增殖自我更新。我们的研究结果提供了支持后一种情况的令人信服的证据，并进一步结合数学模型表明，自我更新是迄今为止新产生的CD 57+记忆T细胞的最丰富来源。因此，免疫记忆在表达CD 57的高度分化的T细胞亚群中似乎是内在可持续的。CD 57+记忆T细胞在体内不是复制性衰老的。CD 57+记忆T细胞主要通过体内自我更新来维持。体外研究已经导致广泛持有的假设，即复制性衰老记忆T细胞表达碳水化合物表位CD 57。使用各种实验方法和数学建模的复合数据集，艾哈迈德等人。显示CD 57+记忆T细胞在体内增殖和自我更新。
A central paradigm in the field of lymphocyte biology asserts that replicatively senescent memory T cells express the carbohydrate epitope CD57. These cells nonetheless accumulate with age and expand numerically in response to persistent antigenic stimulation. Here, we use in vivo deuterium labeling and ex vivo analyses of telomere length, telomerase activity, and intracellular expression of the cell-cycle marker Ki67 to distinguish between two non-exclusive scenarios: (1) CD57+ memory T cells do not proliferate and instead arise via phenotypic transition from the CD57− memory T cell pool; and/or (2) CD57+ memory T cells self-renew via intracompartmental proliferation. Our results provide compelling evidence in favor of the latter scenario and further suggest in conjunction with mathematical modeling that self-renewal is by far the most abundant source of newly generated CD57+ memory T cells. Immunological memory therefore appears to be intrinsically sustainable among highly differentiated subsets of T cells that express CD57. CD57+ memory T cells are not replicatively senescent in vivo CD57+ memory T cells are maintained primarily via self-renewal in vivo In vitro studies have led to the widely held assumption that replicatively senescent memory T cells express the carbohydrate epitope CD57. Using a variety of experimental approaches and mathematical modeling of composite datasets, Ahmed et al. show that CD57+ memory T cells proliferate and self-renew in vivo.
登录
查看更多内容
影响因子：
4.3
作者：
Ahmed R;Westera L;Drylewicz J;Elemans M;Zhang Y;Kelly E;Reljic R;Tesselaar K;de Boer RJ;Macallan DC;Borghans JA;Asquith B
通讯作者：
Asquith B
影响因子：
82.9
作者：
Hellerstein, M;Hanley, MB;McCune, JM
通讯作者：
McCune, JM
影响因子：
3.7
作者：
Bodnar, AG;Kim, NW;Chiu, CP
通讯作者：
Chiu, CP
影响因子：
9.8
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
通讯作者：
Asquith B
影响因子：
15.3
作者：
Casazza, Joseph P.;Betts, Michael R.;Price, David A.;Precopio, Melissa L.;Ruff, Laura E.;Brenchley, Jason M.;Hill, Brenna J.;Roederer, Mario;Douek, Daniel C.;Koup, Richard A.
通讯作者：
Koup, Richard A.