Lck activity controls CD4/CD8 T cell lineage commitment
Lck activity controls CD4/CD8 T cell lineage commitment
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DOI：
10.1016/s1074-7613(00)80184-3
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发表时间：
2000-03-01
期刊：
影响因子：
32.4
通讯作者：
Alberola-Ila, J
中科院分区：
文献类型：
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作者：
Hernández-Hoyos, G;Sohn, SJ;Alberola-Ila, J
携带MHC I类限制性TCR的胸腺细胞分化为dos T细胞，而识别MHC II类的胸腺细胞则成为CD 4 T细胞。MHC类识别、辅助受体表达和效应子功能如何协调的机制还不清楚。由于酪氨酸激酶Lck与CD 4的结合亲和力大于与CD 8的结合亲和力，因此已提出将其作为介导该过程的候选物。通过使用Lck活性改变的转基因小鼠，我们表明，携带II类限制性TCR的胸腺细胞在Lck活性降低时发育成功能性CD 8 T细胞。相反，当Lck活性增加时，携带I类限制性TCR的胸腺细胞发育成功能性CD 4 T细胞。这些结果直接表明Lck信号的定量差异控制着CD 4/CD 8谱系决定。
Thymocytes carrying MHC class I-restricted TCRs differentiate into dos T cells, while those recognizing MHC class II become CD4 T cells. The mechanisms underlying how MHC class recognition, coreceptor expression, and effector function are coordinated are not well understood. Since the tyrosine kinase Lck binds with more affinity to CD4 than CD8, it has been proposed as a candidate to mediate this process. By using transgenic mice with altered Lck activity, we show that thymocytes carrying a class Ii-restricted TCR develop into functional CD8 T cells when Lck activity is reduced. Conversely, thymocytes carrying a class I-restricted TCR develop into functional CD4 T cells when Lck activity is increased. these results directly show that quantitative differences in the Lck signal control the CD4/CD8 lineage decision.