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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats.
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Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats.

机译：与CD4 + 8 +小鼠和大鼠胸腺细胞的CD4 / CD8谱系决定相反的等效触发信号：与小鼠（而非大鼠）中截短的CD8α链的胸腺表达相关。

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摘要

Unselected CD4+8+ rat thymocytes, generated in vitro from their direct precursors, are readily converted to functional TCRhigh T cells by stimulation with immobilized TCR-specific mAb plus IL-2. Lineage decision invariably occurs toward CD4-8+, regardless of the timing of TCR stimulation after entry into the CD4+8+ compartment or the concentration of TCR-specific mAb used for stimulation. CD4-specific mAb synergizes with suboptimal TCR-specific mAb in inducing T cell maturation, but lineage decision remains exclusively CD4-8+. These results contrast with those obtained in mice, in which Abs to the TCR complex were shown to promote CD4+8- T cell maturation from CD4+8+ thymocytes. Surprisingly, when rat and mouse CD4+8+ thymocytes were stimulated with PMA/ionomycin under identical conditions, the opposite lineage commitment was observed, i.e., mouse thymocytes responded with the generation of CD4+8- and rat thymocytes with the generation of CD4-8+ cells. It thus seems that CD4+8+ thymocytes of the two species respond with opposite lineage decisions to strong activating signals such as given by TCR-specific mAb or PMA/ionomycin. A possible key to this difference lies in the availability of p56lck for coreceptor. supported signaling. We show that in contrast to mouse CD4+8+ thymocytes, which express both a complete and a truncated CD8 alpha-chain (CD8 alpha') unable to bind p56lck, rat thymocytes only express full-length CD8 alpha molecules. Mice, but not rats, therefore may use CD8 alpha' as a "dominant negative" coreceptor chain to attenuate the CD8 signal, thereby facilitating MHC class II recognition through the higher amount of p56lck delivered, and rats may use a different mechanism for MHC class distinction during positive selection.
机译：通过固定的TCR特异性mAb加IL-2刺激，从其直接前体体外产生的未选择的CD4 + 8 +大鼠胸腺细胞很容易转化为功能性TCRhigh T细胞。无论进入CD4 + 8 +区室后TCR刺激的时机如何，或用于刺激的TCR特异性mAb的浓度如何，沿CD4-8 +方向始终都会做出血统决定。 CD4特异性mAb在诱导T细胞成熟中与次佳的TCR特异性mAb协同作用，但谱系决定仍然仅是CD4-8 +。这些结果与在小鼠中获得的结果相反，在小鼠中，显示出TCR复合物的Abs可促进CD4 + 8 +胸腺细胞中CD4 + 8-T细胞成熟。出人意料的是，当在相同条件下用PMA /离子霉素刺激大鼠和小鼠CD4 + 8 +胸腺细胞时，观察到相反的谱系承诺，即，小鼠胸腺细胞以CD4 + 8-产生响应，而大鼠胸腺细胞以CD4- +产生。 8个以上的单元格。因此，似乎这两个物种的CD4 + 8 +胸腺细胞以相反的谱系决定响应强激活信号，例如TCR特异性mAb或PMA / ionomycin。造成这种差异的一个可能关键在于共受体p56lck的可用性。支持的信令。我们显示，与小鼠CD4 + 8 +胸腺细胞相反，后者表达无法结合p56lck的完整和截断的CD8α链（CD8 alpha'），而大鼠胸腺细胞仅表达全长CD8α分子。因此，小鼠而不是大鼠，可以使用CD8 alpha'作为“显性负性”共受体链来减弱CD8信号，从而通过传递更高的p56lck量来促进II类MHC的识别，并且大鼠可以对MHC类使用不同的机制积极选择中的区别。

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