Noraz N, Saha K, Ottones F, Smith S, Taylor N
Institut de Génétique Moléculaire de Montpellier, France.
J Immunol. 1998 Mar 1;160(5):2042-5.
Both human T cell leukemia virus type I and simian Herpesvirus saimiri (HVS) transform human T cells in vitro. Although IL-2-independent growth in human T cell leukemia virus type I-transformed T cells is associated with constitutive phosphorylation of JAK/STAT kinases, we now demonstrate that different mechanisms may be responsible for the ability of HVS-transformed T cells to proliferate in the absence of exogenous cytokines. The IL-2 independence of an HVS-transformed cell line correlated with constitutive activation of protein tyrosine kinases known to be induced following TCR engagement. Thus, in these cells we observed increased phosphotransferase activity of Lck as well as constitutive tyrosine phosphorylation of the TCR-associated ZAP-70 kinase and expression of the related Syk protein tyrosine kinase. While Syk is generally not expressed in activated T cells, its introduction has been shown to enhance TCR responsiveness. These results suggest that distinct signal transduction cascades can participate in the transition of T cells to IL-2 independence.
人类I型T细胞白血病病毒和猴疱疹病毒（HVS）均可在体外转化人T细胞。虽然人类I型T细胞白血病病毒转化的T细胞中不依赖白细胞介素-2的生长与JAK/STAT激酶的组成型磷酸化有关，但我们现在证明，不同的机制可能是HVS转化的T细胞在无外源性细胞因子情况下增殖能力的原因。一种HVS转化的细胞系不依赖白细胞介素-2与已知在T细胞受体（TCR）参与后被诱导的蛋白酪氨酸激酶的组成型激活相关。因此，在这些细胞中，我们观察到Lck的磷酸转移酶活性增加，以及TCR相关的ZAP-70激酶的组成型酪氨酸磷酸化和相关的Syk蛋白酪氨酸激酶的表达。虽然Syk通常在活化的T细胞中不表达，但已表明其引入可增强TCR反应性。这些结果表明，不同的信号转导级联可参与T细胞向不依赖白细胞介素-2状态的转变。
