van Oers N S, Lowin-Kropf B, Finlay D, Connolly K, Weiss A
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
Immunity. 1996 Nov;5(5):429-36. doi: 10.1016/s1074-7613(00)80499-9.
Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4+CD8+ thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in these mice, suggesting that additional PTKs may contribute to T cell development. Here we show that the combined disruption of Lck and Fyn (lck(-/-)fyn(-/-)) completely arrests alpha beta T cell development at the CD4-CD8- stage. The development of V gamma 3+ dendritic epidermal T cells is also severely impaired, but natural killer cell development and cytolytic activity is unaffected in lck(-/-)fyn(-/-) mice. These findings reveal the potential for redundant functions mediated by Src family PTKs while emphasizing crucial roles for Lck and Fyn in T cell development.
T细胞发育需要两类蛋白酪氨酸激酶（PTK）家族，即Src家族和Syk/ZAP-70家族。Lck是胸腺生成所需的主要Src家族成员，因为在其缺失时，CD4+CD8+胸腺细胞和成熟T细胞严重缺乏。然而，在这些小鼠中仍有一些外周T细胞，这表明其他PTK可能有助于T细胞发育。在此我们表明，Lck和Fyn的联合缺失（lck(-/-)fyn(-/-)）会使αβT细胞发育在CD4-CD8-阶段完全停滞。Vγ3+树突状表皮T细胞的发育也严重受损，但lck(-/-)fyn(-/-)小鼠的自然杀伤细胞发育和细胞溶解活性不受影响。这些发现揭示了Src家族PTK介导的冗余功能的可能性，同时强调了Lck和Fyn在T细胞发育中的关键作用。
