研究揭示中央記憶CD8+T細胞的來源
作者：
小柯機器人發布時間：2020/11/4 16:43:33
瑞士洛桑大學Werner Held研究小組發現，在溶細胞分化缺失時，中央記憶CD8+T細胞由幹細胞樣Tcf7hi效應細胞產生。這一研究成果於2020年10月30日在線發表在國際學術期刊《免疫》上。
研究人員發現了罕見的效應階段CD8+T細胞，該細胞表達大量的轉錄因子Tcf7（Tcf1），並且沒有顯示出溶細胞分化傾向，並顯示出中央記憶CD8+T細胞（Tcm）的關鍵特徵。根據譜系追蹤，這些效應階段Tcf7hi細胞定量產生了Tcm細胞。
從機制上講，Tcf1抵消了Tcf7hi細胞的分化，並維持了對CD8+T細胞乾性至關重要的保守成年幹細胞基因的表達。在效應子對急性感染的效應反應期間，幹細胞樣CD8+T細胞的發現為優化Tcm細胞的形成提供了機會。
據介紹，Tcm控制全身性繼發感染，並且由於它們具有幹細胞樣的擴增、分化和自我更新能力，因此可以預防慢性感染和癌症。通常認為中樞記憶是在病原體清除後出現，並基於溶細胞效應細胞的去分化而形成。
附：英文原文
Title: Central memory CD8+ T cells derive from stem-like Tcf7hi effector cells in the absence of cytotoxic differentiation
Author: Daniela Pais Ferreira, Joana Gomes Silva, Tania Wyss, Silvia A. Fuertes Marraco, Léonardo Scarpellino, Mélanie Charmoy, Roeltje Maas, Imran Siddiqui, Li Tang, Johanna A. Joyce, Mauro Delorenzi, Sanjiv A. Luther, Daniel E. Speiser, Werner Held
Issue&Volume: 2020-10-30
Abstract: Central memory CD8+ T cells (Tcm) control systemic secondary infections and can protect from chronicinfection and cancer as a result of their stem-cell-like capacity to expand, differentiate,and self-renew. Central memory is generally thought to emerge following pathogen clearanceand to form based on the de-differentiation of cytolytic effector cells. Here, weuncovered rare effector-phase CD8+ T cells expressing high amounts of the transcription factor Tcf7 (Tcf1) that showed no evidence of prior cytolytic differentiation and that displayedkey hallmarks of Tcm cells. These effector-phase Tcf7hi cells quantitatively yielded Tcm cells based on lineage tracing. Mechanistically,Tcf1 counteracted the differentiation of Tcf7hi cells and sustained the expression of conserved adult stem-cell genes that were criticalfor CD8+ T cell stemness. The discovery of stem-cell-like CD8+ T cells during the effector response to acute infection provides an opportunity tooptimize Tcm cell formation by vaccination.
DOI: 10.1016/j.immuni.2020.09.005
Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30399-X