Pingel S, Baker M, Turner M, Holmes N, Alexander D R
Laboratory of Lymphocyte Signalling and Development Programme of Molecular Immunology, The Babraham Institute, Cambridge, GB.
Eur J Immunol. 1999 Aug;29(8):2376-84. doi: 10.1002/(SICI)1521-4141(199908)29:08<2376::AID-IMMU2376>3.0.CO;2-7.
The pre-TCR complex regulates the transition from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP) thymocytes during T cell development. In CD45(-/-) mice there is an accumulation of DN cells, suggesting a possible role for CD45 in pre-TCR signaling. We therefore crossed CD45(-/-) with Rag-1(-/-) mice to investigate the signaling functions of the CD3 complex in DN thymocytes. Remarkably, treatment of Rag-1(-/-)/CD45(-/-) mice with a CD3 mAb caused maturation to the DP stage at only 3% of the level measured in Rag-1(-/-) mice. Furthermore, ligation of the CD3 complex on Rag-1(-/-) /CD45(-/-) thymocytes in vitro induced less tyrosine phosphorylation in specific proteins when compared to Rag-1(-/-) thymocytes. CD45(-/-) mice were also crossed with pLGFA mice expressing a constitutively active form of the lck tyrosine kinase which restored the DN to DP transition to near normal levels. Our results are consistent with a model in which CD45-activated p56(lck) is critical for pre-TCR signal transduction.
前T细胞受体复合物在T细胞发育过程中调节从CD4(-)CD8(-)双阴性（DN）胸腺细胞到CD4(+)CD8(+)双阳性（DP）胸腺细胞的转变。在CD45(-/-)小鼠中，DN细胞会积累，这表明CD45在前T细胞受体信号传导中可能发挥作用。因此，我们将CD45(-/-)小鼠与Rag-1(-/-)小鼠杂交，以研究DN胸腺细胞中CD3复合物的信号传导功能。值得注意的是，用CD3单克隆抗体处理Rag-1(-/-)/CD45(-/-)小鼠，其成熟到DP阶段的水平仅为Rag-1(-/-)小鼠中测得水平的3%。此外，与Rag-1(-/-)胸腺细胞相比，体外连接Rag-1(-/-)/CD45(-/-)胸腺细胞上的CD3复合物会导致特定蛋白质中的酪氨酸磷酸化减少。CD45(-/-)小鼠还与表达组成型活性形式的lck酪氨酸激酶的pLGFA小鼠杂交，这使DN到DP的转变恢复到接近正常水平。我们的结果与一个模型一致，即CD45激活的p56(lck)在前T细胞受体信号转导中至关重要。
