Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1.
Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1.
复制标题
DOI：
10.1016/j.celrep.2018.03.020
复制
发表时间：
2018-03-27
期刊：
影响因子：
8.8
通讯作者：
Hedrick SM
中科院分区：
文献类型：
--
作者：
Utzschneider DT;Delpoux A;Wieland D;Huang X;Lai CY;Hofmann M;Thimme R;Hedrick SM
急性缓解感染后的免疫或慢性病毒感染的长期平衡通常依赖于抗原特异性CD8+T细胞的维持，但这些细胞正在进行的转录要求仍不清楚。我们证明，FOXO1的主动和连续编程对于内存种群的功能维护是必需的。当感染缓解后Foxo1基因缺失时，记忆细胞迅速失去其特有的基因表达，数量逐渐减少，自我更新受损。这被扩展到慢性感染，因为在持续的病毒感染期间FOXO1的丢失导致Tcf7(也就是。TCF1)-表达类似记忆的CD8+T细胞亚群。我们进一步确定FOXO1调节是人类记忆CD8+T细胞的特征。总体而言，我们表明记忆T细胞群体的分子和功能寿命是由转录因子FOXO1积极维持的。Utzschneider等人。研究发现，CD8+T细胞记忆的特征，如长寿、自我更新，以及在静止和细胞分裂之间循环的能力，依赖于FOXO1的持续表达。在这些阶段中的任何一个阶段，FOXO1的丢失都会导致T细胞记忆中断。
Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programming by FOXO1 is required for the functional maintenance of a memory population. Upon Foxo1 deletion following resolution of an infection, memory cells rapidly lost their characteristic gene expression, gradually declined in number, and were impaired in self-renewal. This was extended to chronic infections, as a loss of FOXO1 during a persistent viral infection led to a rapid decline of the TCF7 (a.k.a. TCF1)-expressing memory-like subset of CD8+ T cells. We further establish FOXO1 regulation as a characteristic of human memory CD8+ T cells. Overall, we show that the molecular and functional longevity of a memory T cell population is actively maintained by the transcription factor FOXO1. Utzschneider et al. find that hallmarks of CD8+ T cell memory such as longevity, self-renewal, and the ability to cycle between quiescence and cell division depend on continued expression of FOXO1. Loss of FOXO1 during any of these stages leads to the interruption of T cell memory.
登录
查看更多内容
DOI：
10.1084/jem.20142237
发表时间：
2015-06-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Odorizzi PM;Pauken KE;Paley MA;Sharpe A;Wherry EJ
通讯作者：
Wherry EJ
影响因子：
32.4
作者：
Kim MV;Ouyang W;Liao W;Zhang MQ;Li MO
通讯作者：
Li MO
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C