Migita K, Eguchi K, Kawabe Y, Nagataki S
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Immunology. 1995 Aug;85(4):550-5.
T-cell antigen receptor (TCR), which is not itself a protein tyrosine kinase (PTK), is thought to be associated with at least two SRC-like PTKs, P59fyn and ZAP-70. Activation of these PTKs is required for T-cell signal transduction. The aim of the present study was to determine the roles of PTKs in peripheral T-cell activation, induced by in vivo bacterial superantigen administration. We demonstrated that in vivo staphylococcal enterotoxin B (SEB) administration induced an enhanced tyrosine phosphorylation in peripheral spleen T cells undergoing a programmed cell death. In vitro immunecomplex kinase assay using antibody against P59fyn showed increased fyn kinase activity in SEB-stimulated spleen T cells. We examined the effect of PTK-specific inhibitors on DNA fragmentation and programmed cell death of V beta 8 positive T cells following in vitro culture of SEB-primed spleen T cells. Our results indicated that pretreatment of SEB-activated T cells with PTK inhibitors reduced DNA fragmentation and programmed cell death of V beta 8 positive T cells. These findings suggest that PTK plays an important role in activation and apoptosis of peripheral T cells induced by in vivo SEB administration.
T细胞抗原受体（TCR）本身并非蛋白酪氨酸激酶（PTK），但被认为与至少两种Src样PTK，即P59fyn和ZAP - 70相关联。这些PTK的激活是T细胞信号转导所必需的。本研究的目的是确定PTK在体内给予细菌超抗原诱导的外周T细胞激活中的作用。我们证明，体内给予葡萄球菌肠毒素B（SEB）可诱导经历程序性细胞死亡的外周脾T细胞中酪氨酸磷酸化增强。使用抗P59fyn抗体进行的体外免疫复合物激酶测定显示，SEB刺激的脾T细胞中fyn激酶活性增加。我们检测了PTK特异性抑制剂对SEB预处理的脾T细胞体外培养后Vβ8阳性T细胞DNA片段化和程序性细胞死亡的影响。我们的结果表明，用PTK抑制剂预处理SEB激活的T细胞可减少Vβ8阳性T细胞的DNA片段化和程序性细胞死亡。这些发现表明，PTK在体内给予SEB诱导的外周T细胞激活和凋亡中起重要作用。
