Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors.
Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors.
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DOI：
10.1084/jem.20071855
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发表时间：
2008-01-21
期刊：
影响因子：
--
通讯作者：
Hengartner H
中科院分区：
文献类型：
--
作者：
Löhning M;Hegazy AN;Pinschewer DD;Busse D;Lang KS;Höfer T;Radbruch A;Zinkernagel RM;Hengartner H
许多疫苗接种策略和免疫细胞疗法旨在增加对保护性抗原有反应的记忆 T 细胞的数量。然而，CD4 记忆细胞的分化谱系以及最佳生成条件仍然存在争议。线性和发散分化模型已被提出，表明 CD4 记忆 T 细胞分别从幼稚前体发育而来，无论有或没有效应阶段中间体。在这里，我们通过使用新的技术来识别和分离分泌效应细胞因子的效应 T 细胞来解决这个问题。在将细胞过继转移到正常、非淋巴细胞减少的小鼠中时，我们发现，在体外或体内激发的纯化干扰素γ分泌T辅助细胞（Th）1型和白细胞介素（IL）-4或IL-10分泌Th2效应细胞可以有效地产生长寿命的病毒特异性记忆T细胞。重要的是，这种效应源性记忆 T 细胞在病毒攻击感染中发挥作用。它们增殖旺盛，快速调节 IL-7 受体表达，表现出细胞因子模式的部分稳定性和灵活性，并对病毒诱导的免疫病理学产生不同的影响。因此，细胞因子分泌效应细胞可以逃避激活诱导的细胞死亡并发育成长寿命的功能性记忆细胞。这些发现证明了线性记忆 T 细胞分化的效率，并鼓励基于分化的效应 T 细胞设计疫苗和免疫细胞疗法。
Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation models have been proposed, suggesting CD4 memory T cell development from naive precursors either with or without an effector-stage intermediate, respectively. Here, we address this question by using newly available techniques for the identification and isolation of effector T cells secreting effector cytokines. In adoptive cell transfers into normal, nonlymphopenic mice, we show that long-lived virus-specific memory T cells can efficiently be generated from purified interferon γ–secreting T helper (Th) type 1 and interleukin (IL)-4– or IL-10–secreting Th2 effectors primed in vitro or in vivo. Importantly, such effector-derived memory T cells were functional in viral challenge infections. They proliferated vigorously, rapidly modulated IL-7 receptor expression, exhibited partial stability and flexibility of their cytokine patterns, and exerted differential effects on virus-induced immunopathology. Thus, cytokine-secreting effectors can evade activation-induced cell death and develop into long-lived functional memory cells. These findings demonstrate the efficiency of linear memory T cell differentiation and encourage the design of vaccines and immune cell therapies based on differentiated effector T cells.
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DOI：
10.1084/jem.182.5.1357
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Openshaw P;Murphy EE;Hosken NA;Maino V;Davis K;Murphy K;O'Garra A
通讯作者：
O'Garra A
DOI：
10.1084/jem.20070041
发表时间：
2007-09-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
McKinstry KK;Golech S;Lee WH;Huston G;Weng NP;Swain SL
通讯作者：
Swain SL
影响因子：
4.4
作者：
Krawczyk, Connie M.;Shen, Hao;Pearce, Edward J.
通讯作者：
Pearce, Edward J.
影响因子：
15.3
作者：
ZINKERNAGEL, RM;HAENSELER, E;ALTHAGE, A
通讯作者：
ALTHAGE, A
影响因子：
30.5
作者：
Wu, CY;Kirman, JR;Seder, RA
通讯作者：
Seder, RA