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T中枢记忆前体可控制克隆优势
2020-10-27 15:46

德国慕尼黑工业大学(TUM) Veit R. Buchholz研究组取得最新进展。他们发现T中枢记忆前体的早期出现可在慢性病毒感染过程中控制克隆优势。这一研究成果于2020年10月26日发表在《自然-免疫学》杂志上。

通过绘制源自单个幼稚前体的CD8 + T细胞家族的长期发育,他们发现在鼠慢性巨细胞病毒(CMV)感染的急性期做出的命运决定可以使记忆膨胀水平改变1000倍以上。与直觉相反,T细胞家族记忆膨胀的能力并不取决于其最初的扩张。

相反,那些占主导地位的慢性感染阶段的罕见T细胞家族表现出类似于已建立的T中枢记忆细胞的早期转录组特征。因此,T细胞家族的长期优势可以通过其T中枢记忆前体的早期含量来精准预测,T中枢记忆前体的早期含量可作为干细胞样记忆膨胀来源。

据悉,CMV感染导致大量CMV特异性T细胞群体的长期维持,这种所谓的“记忆膨胀”的程度主要取决于慢性感染阶段的抗原刺激。

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

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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