Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life.
Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life.
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DOI：
10.4049/jimmunol.1400553
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Rudd BD
中科院分区：
文献类型：
--
作者：
Smith NL;Wissink E;Wang J;Pinello JF;Davenport MP;Grimson A;Rudd BD
新生儿通常对细胞内病原体产生不完全的免疫力，尽管这种缺陷的机制尚不清楚。一个重要的问题是新生儿记忆 CD8+ T 细胞发育受损是否是由于启动环境不成熟或淋巴细胞固有缺陷所致。在这里，我们发现，新生儿和成人 CD8+ T 细胞在同一宿主中对等量的刺激做出反应时会采取不同的命运。成年 CD8+ T 细胞分化为效应细胞和记忆细胞的异质库，而新生儿 CD8+ T 细胞优先产生短寿命的效应细胞，并表现出独特的基因表达谱。令人惊讶的是，新生儿记忆形成受损并不是由于缺乏反应性，而是因为新生儿 CD8+ T 细胞比成人细胞增殖更快，并很快分化为终末细胞。总的来说，这些发现表明新生儿 CD8+ T 细胞在效应细胞和记忆 CD8+ T 细胞分化方面表现出不平衡，这会损害生命早期记忆 CD8+ T 细胞的形成。
Neonates often generate incomplete immunity against intracellular pathogens, although the mechanism of this defect is poorly understood. An important question is whether the impaired development of memory CD8+ T cells in neonates is due to an immature priming environment or lymphocyte-intrinsic defects. Here we show that neonatal and adult CD8+ T cells adopted different fates when responding to equal amounts of stimulation in the same host. While adult CD8+ T cells differentiated into a heterogeneous pool of effector and memory cells, neonatal CD8+ T cells preferentially gave rise to short-lived effector cells and exhibited a distinct gene expression profile. Surprisingly, impaired neonatal memory formation was not due to a lack of responsiveness, but instead because neonatal CD8+ T cells expanded more rapidly than adult cells and quickly became terminally differentiated. Collectively, these findings demonstrate that neonatal CD8+ T cells exhibit an imbalance in effector and memory CD8+ T cell differentiation, which impairs the formation of memory CD8+ T cells in early life.
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DOI：
10.4049/jimmunol.0901481
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kollmann TR;Crabtree J;Rein-Weston A;Blimkie D;Thommai F;Wang XY;Lavoie PM;Furlong J;Fortuno ES 3rd;Hajjar AM;Hawkins NR;Self SG;Wilson CB
通讯作者：
Wilson CB
影响因子：
5.4
作者：
Belnoue, Elodie;Fontannaz-Bozzotti, Paola;Siegrist, Claire-Anne
通讯作者：
Siegrist, Claire-Anne
影响因子：
82.9
作者：
Chang, J;Braciale, TJ
通讯作者：
Braciale, TJ
影响因子：
12.3
作者：
Kim D;Pertea G;Trapnell C;Pimentel H;Kelley R;Salzberg SL
通讯作者：
Salzberg SL
DOI：
10.1084/jem.20071371
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lee HH;Hoeman CM;Hardaway JC;Guloglu FB;Ellis JS;Jain R;Divekar R;Tartar DM;Haymaker CL;Zaghouani H
通讯作者：
Zaghouani H