T中樞記憶前體可控制克隆優勢
作者：
小柯機器人發布時間：2020/10/27 15:46:03
德國慕尼黑工業大學(TUM) Veit R. Buchholz研究組取得最新進展。他們發現T中樞記憶前體的早期出現可在慢性病毒感染過程中控制克隆優勢。這一研究成果於2020年10月26日發表在《自然-免疫學》雜誌上。
通過繪製源自單個幼稚前體的CD8 + T細胞家族的長期發育，他們發現在鼠慢性巨細胞病毒（CMV）感染的急性期做出的命運決定可以使記憶膨脹水平改變1000倍以上。與直覺相反，T細胞家族記憶膨脹的能力並不取決於其最初的擴張。
相反，那些佔主導地位的慢性感染階段的罕見T細胞家族表現出類似於已建立的T中樞記憶細胞的早期轉錄組特徵。因此，T細胞家族的長期優勢可以通過其T中樞記憶前體的早期含量來精準預測，T中樞記憶前體的早期含量可作為幹細胞樣記憶膨脹來源。
據悉，CMV感染導致大量CMV特異性T細胞群體的長期維持，這種所謂的「記憶膨脹」的程度主要取決於慢性感染階段的抗原刺激。
附：英文原文
Title: Early emergence of T central memory precursors programs clonal dominance during chronic viral infection
Author: Simon Grassmann, Lorenz Mihatsch, Jonas Mir, Atefeh Kazeroonian, Roza Rahimi, Sophie Flommersfeld, Kilian Schober, Inge Hensel, Justin Leube, Ludwig O. Pachmayr, Lorenz Kretschmer, Qin Zhang, Adrien Jolly, M. Zeeshan Chaudhry, Matthias Schiemann, Luka Cicin-Sain, Thomas Hfer, Dirk H. Busch, Michael Flossdorf, Veit R. Buchholz
Issue&Volume: 2020-10-26
Abstract: Chronic cytomegalovirus (CMV) infection leads to long-term maintenance of extraordinarily large CMV-specific T cell populations. The magnitude of this so-called 『memory inflation』 is thought to mainly depend on antigenic stimulation during the chronic phase of infection. However, by mapping the long-term development of CD8+ T cell families derived from single naive precursors, we find that fate decisions made during the acute phase of murine CMV infection can alter the level of memory inflation by more than 1,000-fold. Counterintuitively, a T cell family’s capacity for memory inflation is not determined by its initial expansion. Instead, those rare T cell families that dominate the chronic phase of infection show an early transcriptomic signature akin to that of established T central memory cells. Accordingly, a T cell family’s long-term dominance is best predicted by its early content of T central memory precursors, which later serve as a stem-cell-like source for memory inflation. T cell memory formation is often described as occurring during the chronic phases of infection.
DOI: 10.1038/s41590-020-00807-y
Source: https://www.nature.com/articles/s41590-020-00807-y