Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells.
Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells.
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人类天真，中央记忆和效应记忆CD4（+）T细胞的细胞因子驱动的增殖和分化。
DOI：
10.1084/jem.194.12.1711
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发表时间：
2001-12-17
影响因子：
15.3
通讯作者：
Lanzavecchia, A
中科院分区：
文献类型：
--
作者：
Geginat, J;Sallusto, F;Lanzavecchia, A
记忆性T淋巴细胞在抗原不存在的情况下在体内增殖，维持具有不同效应子功能和归巢能力的中央记忆性T细胞（TCM）和效应子记忆性T细胞（TEM）的库。我们比较了人CD 4+幼稚T细胞、TCM细胞和TEM细胞对细胞因子的增殖反应能力，这些细胞因子与T细胞稳态有关。白细胞介素（IL）-7和IL-15以非常高的效率TEM扩增，而TCM的响应性较低，并且初始T细胞未能响应。树突状细胞（DC）和DC衍生的细胞因子允许幼稚T细胞响应于IL-4而选择性增殖，并且通过增加IL-2/IL-15 R β和共同γ链（γc）的表达而有效地增强TCM对IL-7和IL-15的响应。细胞外信号调节激酶和p38丝裂原活化蛋白（MAP）激酶分别选择性地需要TCR和精氨酸驱动的增殖。重要的是，在精氨酸驱动的培养物中，一些增殖的TCM分化为TEM样细胞，获得效应子功能并将趋化因子受体表达从CCR 7转换为CCR 5。持续的抗原非依赖性产生的TEM从一个池的TCM细胞提供了一个合理的机制，多克隆和功能多样的人CD 4+记忆T细胞的库的维护。
Memory T lymphocytes proliferate in vivo in the absence of antigen maintaining a pool of central memory T cells (TCM) and effector memory T cells (TEM) with distinct effector function and homing capacity. We compared human CD4+ naive T, TCM, and TEM cells for their capacity to proliferate in response to cytokines, that have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded with very high efficiency TEM, while TCM were less responsive and naive T cells failed to respond. Dendritic cells (DCs) and DC-derived cytokines allowed naive T cells to proliferate selectively in response to IL-4, and potently boosted the response of TCM to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rβ and the common γ chain (γc). The extracellular signal regulated kinase and the p38 mitogen-activated protein (MAP) kinases were selectively required for TCR and cytokine-driven proliferation, respectively. Importantly, in cytokine-driven cultures, some of the proliferating TCM differentiated to TEM-like cells acquiring effector function and switching chemokine receptor expression from CCR7 to CCR5. The sustained antigen-independent generation of TEM from a pool of TCM cells provides a plausible mechanism for the maintenance of a polyclonal and functionally diverse repertoire of human CD4+ memory T cells.