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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Functional similarity and differences between selection-independent CD4-CD8- alphabeta T cells and positively selected CD8 T cells expressing the same TCR and the induction of anergy in CD4-CD8- alphabeta T cells in antigen-expressing mice.
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Functional similarity and differences between selection-independent CD4-CD8- alphabeta T cells and positively selected CD8 T cells expressing the same TCR and the induction of anergy in CD4-CD8- alphabeta T cells in antigen-expressing mice.

机译:选择无关的CD4-CD8-字母T细胞与表达相同TCR的阳性选择的CD8 T细胞之间的功能相似性和差异,以及在表达抗原的小鼠中CD4-CD8-字母T细胞中无反应性的诱导。

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摘要

In TCR-alphabeta transgenic mice, CD4-CD8- TCR-alphabeta+ (alphabeta DN) cells arise in the absence of positively selecting MHC molecules and are resistant to clonal deletion in Ag-expressing mice. In this study the activation requirements and functional properties of alphabeta double-negative (DN) cells were compared with those of positively selected CD8+ cells expressing equivalent levels of the same MHC class I-restricted transgenic TCR. We found that positively selected CD8+ cells required a lower density of the antigenic ligand for optimal proliferative responses compared with alphabeta DN cells derived from nonpositively selecting mice. However, when the CD8 coreceptor on CD8+ cells was blocked with an anti-CD8 mAb, both alphabeta DN and CD8+ cells exhibited the same dose-response curve to the antigenic ligand and the same dependence on CD28/B7 costimulation. Positively selected CD8+ cells also differed from alphabeta DN cells in that they differentiated into more efficient killers and IL-2 producers after Ag stimulation, even after CD8 blockade. However, Ag-activated alphabeta DN and CD8+ cells were equally efficient in producing IFN-gamma, suggesting that this functional property is independent of positive selection. We also found that alphabeta DN cells recovered from the lymph nodes of Ag-expressing mice were functionally anergic. This anergic state was associated with defective proliferation and IL-2 production in response to Ag stimulation. These observations indicate that alphabeta DN cells can be anergized in vivo by physiological levels of the antigenic ligand.
机译:在TCR-alphabeta转基因小鼠中,CD4-CD8- TCR-alphabeta +(alphabeta DN)细胞在没有阳性选择MHC分子的情况下出现,并且对表达Ag的小鼠的克隆缺失有抵抗力。在这项研究中,将字母双阴性(DN)细胞的激活要求和功能特性与表达相同水平的相同MHC I类限制性转基因TCR的阳性选择的CD8 +细胞进行了比较。我们发现,与源自非阳性选择小鼠的字母DN细胞相比,阳性选择的CD8 +细胞需要较低的抗原配体密度才能实现最佳增殖反应。但是,当用抗CD8 mAb阻断CD8 +细胞上的CD8共受体时,字母DN和CD8 +细胞对抗原配体均表现出相同的剂量反应曲线,并且对CD28 / B7共刺激的依赖性也相同。阳性选择的CD8 +细胞也不同于字母DN细胞,因为在Ag刺激后,即使在CD8阻断后,它们也可以分化为更有效的杀手和IL-2产生者。但是,Ag激活的字母DN和CD8 +细胞在产生IFN-γ方面同样有效,表明该功能特性与阳性选择无关。我们还发现,从表达Ag的小鼠淋巴结中回收的Alphabet DN细胞在功能上是无反应的。这种无反应状态与响应Ag刺激的增殖缺陷和IL-2产生有关。这些观察结果表明,通过生理学水平的抗原配体可以在体内对字母链DN细胞进行厌氧处理。

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