Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs.
Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs.
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人T细胞的稳态膨胀和表型转化取决于与APC的外周相互作用。
DOI：
10.4049/jimmunol.0901711
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Sykes M
中科院分区：
文献类型：
--
作者：
Onoe T;Kalscheuer H;Chittenden M;Zhao G;Yang YG;Sykes M
淋巴细胞减少宿主的免疫恢复在很大程度上取决于稳态外周扩张，特别是当胸腺生成不足时，这在成人中经常发生。虽然已经在小鼠中进行了很好的研究，但由于缺乏适当的体内模型，对人T细胞的稳态外周扩增的研究受到限制。在这里，我们使用T细胞缺陷的人源化小鼠和过继转移的方法来证明两种不同的自体T细胞的增殖反应发生在体内淋巴细胞减少的设置。经历快速增殖的人幼稚CD 4和CD 8 T细胞获得记忆样表型和快速产生IFN-γ的能力，而经历缓慢增殖的人幼稚CD 4和CD 8 T细胞保留幼稚表型和功能特征。两个群体的恢复取决于受体人源化小鼠外周中人非T细胞嵌合的程度。此外，CD 4和CD 8 T细胞的记忆转换分别与受体小鼠中人CD 14+和CD 19+嵌合体的水平相关，表明不同类型的APC支持CD 4和CD 8 T细胞的记忆转换。由于淋巴细胞减少症影响临床结局，因此该模型应允许详细研究淋巴细胞减少症对患者的影响。
Immune recovery in lymphopenic hosts depends largely on homeostatic peripheral expansion, especially when thymopoiesis is insufficient, as is often the case in human adults. While it has been well studied in mice, the study of homeostatic peripheral expansion of human T cells has been limited by the lack of an appropriate in vivo model. Here, we use T cell-deficient humanized mice and an adoptive transfer approach to demonstrate that two distinct proliferative responses of autologous T cells occur in vivo in a lymphopenic setting. Human naïve CD4 and CD8 T cells that undergo rapid proliferation acquire a memory-like phenotype and the ability to rapidly produce IFN-γ, while those undergoing slow proliferation retain naïve phenotypic and functional characteristics. Recovery of both populations depends on the extent of human non-T cell chimerism in the periphery of recipient humanized mice. Furthermore, memory conversion of CD4 and CD8 T cells correlates with the level of human CD14+ and CD19+ chimerism in recipient mice, respectively, suggesting that different types of APCs support memory conversion of CD4 and CD8 T cells. Since lymphopenia affects clinical outcomes, this model should allow detailed investigation of the effects of lymphopenia in patients.
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影响因子：
64.8
作者：
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