Tetracycline-controllable selection of CD4+ T cells:: Half-life and survival signals in the absence of major histocompatibility complex class II molecules

Tetracycline-controllable selection of CD4+ T cells:: Half-life and survival signals in the absence of major histocompatibility complex class II molecules
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DOI:
10.1084/jem.191.2.355
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发表时间:
2000-01-17
影响因子:
15.3
通讯作者:
Mathis, D
Mathis, D
中科院分区:
医学1区
文献类型:
--
作者:
Witherden, D;van Oers, N;Mathis, D

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一个系统,允许研究,在一个温和的方式,MHC分子在幼稚T细胞存活的作用被描述。主要组织相容性复合物ii类缺陷小鼠以四环素(tet)可控的方式仅在胸腺上皮细胞中表达E α链。这导致细胞表面E复合物的反应性显示,CD4(+)8(-)胸腺细胞的阳性选择,以及CD4(+) T细胞的产生,在ii类贫瘠的外周区。使用该系统,我们已经解决了两个尚未解决的问题:缺乏II类分子的初始CD4(+) T细胞的半衰期(3-4周)和初始CD4(+) T细胞参与II类分子相关的早期信号事件(部分CD3 zeta链磷酸化和ZAP-70关联)。
A system that allows the study, in a gentle fashion, of the role of MHC molecules in naive T cell survival is described. Major histocompatibility complex class II-deficient mice were engineered to express E alpha chains only in thymic epithelial cells in a tetracycline (tet)-controllable manner. This resulted in tet-responsive display of cell surface E complexes, positive selection of CD4(+)8(-) thymocytes, and generation of a CD4(+) T cell, compartment in a class II-barren periphery. Using this system, we have addressed two unresolved issues: the half-life of naive CD4(+) T cells in the absence of class II molecules (3-4 wk) and the early signaling events associated with class II molecule engagement by naive CD4(+) T cells (partial CD3 zeta chain phosphorylation and ZAP-70 association).