Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules.
Peripheral T cell survival requires continual ligation of the T cell receptor to major histocompatibility complex-encoded molecules.
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DOI：
10.1084/jem.186.8.1269
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发表时间：
1997-10-20
期刊：
影响因子：
--
通讯作者：
von Boehmer H
中科院分区：
文献类型：
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作者：
Kirberg J;Berns A;von Boehmer H
在胸腺中，根据T细胞受体（TCR）特异性选择T细胞。在阳性选择后，成熟细胞从初级淋巴器官输出以接种次级淋巴组织。一个重要的问题是，成熟T细胞的存活是一种内在特性还是需要连续的存活信号，即，TCR与外周中的主要组织相容性复合体（MHC）分子的接合，可能以与胸腺阳性选择期间发生的类似方式。为了解决这个问题，我们使用重组激活基因（Rag）缺陷型H-2b小鼠表达受I-Ed II类MHC分子限制的转基因TCR。植入Rag-/-H-2d胎儿胸腺后，出现CD 4 +8-外周T细胞。将这些细胞分离并转移到H-2b或H-2d单倍型的免疫缺陷宿主中，后者中的一些是常见细胞因子受体γ链缺陷的，以排除宿主自然杀伤细胞对H-2b供体细胞的排斥。我们的研究结果表明，在没有，但不是在存在的情况下，选择的MHC分子，外周成熟T细胞是短暂的，并在7周内消失，表明持续接触的TCR与选择的MHC分子是T细胞的生存所必需的。
In the thymus, T cells are selected according to their T cell receptor (TCR) specificity. After positive selection, mature cells are exported from primary lymphoid organs to seed the secondary lymphoid tissue. An important question is whether survival of mature T cells is an intrinsic property or requires continuous survival signals, i.e., engagement of the TCR by major histocompatibility complex (MHC) molecules in the periphery, perhaps in a similar way as occurring during thymic positive selection. To address this issue we used recombination-activating gene (Rag)-deficient H-2b mice expressing a transgenic TCR restricted by I-Ed class II MHC molecules. After engraftment with Rag−/− H-2d fetal thymi, CD4+8− peripheral T cells emerged. These cells were isolated and transferred into immunodeficient hosts of H-2b or H-2d haplotype, some of the latter being common cytokine receptor γ chain deficient to exclude rejection of H-2b donor cells by host natural killer cells. Our results show that in the absence, but not in the presence, of selecting MHC molecules, peripheral mature T cells are short lived and disappear within 7 wk, indicating that continuous contact of the TCR with selecting MHC molecules is required for survival of T cells.