Chaffin K E, Beals C R, Wilkie T M, Forbush K A, Simon M I, Perlmutter R M
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
EMBO J. 1990 Dec;9(12):3821-9. doi: 10.1002/j.1460-2075.1990.tb07600.x.
Stimulation of the T lymphocyte antigen receptor-CD3 complex (TCR-CD3) causes T cell activation by a process associated with increased phosphatidylinositol-specific phospholipase C (PI-PLC) activity. Evidence exists suggesting that GTP-binding (G) proteins, particularly the pertussis toxin (PT)-sensitive Gi proteins, participate in this signal transduction pathway. To clarify the role of Gi proteins in TCR-CD3 signaling, and to investigate other possible functions of Gi molecules in T cells, we expressed the S1 subunit of PT in the thymocytes of transgenic mice using the lymphocyte-specific lck promoter. Transgenic thymocytes contained S1 activity and exhibited profound depletion of Gi protein PT substrates in a manner suggesting their inactivation by S1 in vivo. Nevertheless, treatment of transgenic thymocytes with mitogenic stimuli provoked normal increases in intracellular free Ca2+ concentrations and IL-2 secretion, indicating that Gi proteins are not required for T cell activation. These normal signaling responses notwithstanding, mature thymocytes accumulated in lck-PT mice and did not appear in secondary lymphoid organs or in the circulation. Viewed in the context of the known features of Bordetella pertussis infection, our results suggest that a PT-sensitive signaling process, probably involving Gi proteins, regulates thymocyte emigration.
T淋巴细胞抗原受体-CD3复合物（TCR-CD3）的刺激通过与磷脂酰肌醇特异性磷脂酶C（PI-PLC）活性增加相关的过程导致T细胞活化。有证据表明，GTP结合（G）蛋白，特别是百日咳毒素（PT）敏感的Gi蛋白，参与了这一信号转导途径。为了阐明Gi蛋白在TCR-CD3信号传导中的作用，并研究Gi分子在T细胞中的其他可能功能，我们使用淋巴细胞特异性lck启动子在转基因小鼠的胸腺细胞中表达PT的S1亚基。转基因胸腺细胞含有S1活性，并以提示其在体内被S1灭活的方式表现出Gi蛋白PT底物的显著消耗。然而，用促有丝分裂刺激物处理转基因胸腺细胞会引起细胞内游离Ca2+浓度和IL-2分泌的正常增加，表明T细胞活化不需要Gi蛋白。尽管有这些正常的信号反应，但成熟胸腺细胞在lck-PT小鼠中积累，并未出现在二级淋巴器官或循环中。结合百日咳博德特氏菌感染的已知特征来看，我们的结果表明，一个可能涉及Gi蛋白的PT敏感信号过程调节胸腺细胞的迁出。
