Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
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DOI：
10.1038/44385
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发表时间：
1999-10-14
期刊：
影响因子：
64.8
通讯作者：
Lanzavecchia, A
中科院分区：
文献类型：
--
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
幼稚T淋巴细胞移动到次级淋巴器官的T细胞区域，寻找树突状细胞呈递的抗原（1，2）。一旦被激活，它们就会剧烈增殖，产生可以迁移到B细胞区域或炎症组织的效应细胞（3-6）。一部分引发的T淋巴细胞作为循环记忆细胞持续存在，可以提供保护，并在二次攻击时提供定性不同和定量增强的反应（7-9）介导免疫记忆不同方面的细胞的性质尚未解决。在这里，我们表明，CCR 7的表达，趋化因子受体，控制归巢到次级淋巴器官，分为两个功能不同的人类记忆T细胞亚群，CCR 7（-）记忆细胞表达受体迁移到发炎组织和显示即时效应功能。相反，CCR 7（+）记忆细胞表达淋巴结归巢受体，缺乏立即效应功能，但有效地刺激树突状细胞，并在二次刺激后分化为CCR 7（-）效应细胞。CCR 7（+）和CCR 7（-）T细胞，我们将其命名为中央记忆（T-CM）和效应记忆（T-EM），以逐步的方式从幼稚T细胞分化，在免疫后持续多年，并允许在记忆反应中进行分工。
Naive T lymphocytes travel to T-cell areas of secondary lymphoid organs in search of antigen presented by dendritic cells(1,2). Once activated, they proliferate vigorously, generating effector cells that can migrate to B-cell areas or to inflamed tissues(3-6). A fraction of primed T lymphocytes persists as circulating memory cells that can confer protection and give, upon secondary challenge, a qualitatively different and quantitatively enhanced response(7-9) The nature of the cells that mediate the different facets of immunological memory remains unresolved. Here we show that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets, CCR7(-) memory cells express receptors for migration to inflamed tissues and display immediate effector function. In contrast, CCR7(+) memory cells express lymph-node homing receptors and lack immediate effector function, but efficiently stimulate dendritic cells and differentiate into CCR7(-) effector cells upon secondary stimulation. The CCR7(+) and CCR7(-) T cells, which we have named central memory (T-CM) and effector memory (T-EM), differentiate in a step-wise fashion from naive T cells, persist for years after immunization and allow a division of labour in the memory response.