Dissociation of phosphoinositide hydrolysis and Ca2+ fluxes from the biological responses of a T-cell hybridoma-猫眼课题宝

T 细胞杂交瘤生物反应中磷酸肌醇水解和 Ca2 通量的解离

DOI：

10.1038/334625a0

发表时间：

1988

期刊：

Nature

影响因子：

64.8

通讯作者：

中科院分区：

综合性期刊1区

文献类型：

作者：

J. Sussman;M. Merćep;T. Saito;R. Germain;E. Bonvini;J. Ashwell

T淋巴细胞可以通过多种方式被激活，包括占用T细胞抗原受体（TCR）复合物或某些细胞表面分子与抗体1 - 4交联。刺激后最早的两个事件是磷脂酰肌醇二磷酸水解为肌醇三磷酸（Ins P3）和1,2-二酰基甘油（DAG） 5-7，细胞内Ca2+ ([Ca2+]i)浓度增加8-11。随后，细胞分泌淋巴因子并表达淋巴因子受体1。据推测，磷脂酰肌醇（Ptd Ins）的水解产物和[Ca2+]i的波动是关键的“第二信使”≈，为后续事件的启动传递信号。我们研究了这些第二信使和IL-2分泌之间的关系，在小鼠T细胞变体中，缺失的TCR复合物通过基因转移被重建。令人惊讶的是，尽管转染物的IL-2反应无法与表达相同TCR的原始细胞系区分，但在重组细胞中，Ptd - Ins水解和[Ca2+]i的增加大幅减少或不存在。因此，有可能将这些早期生化变化与晚期生物反应分离开来，从而对这些事件的假定因果关系提出质疑。

T lymphocytes can be activated in a variety of ways, including occupancy of the T cell antigen receptor (TCR) complex or cross-linking of certain cell-surface molecules with antibody1–4. Two of the earliest events seen after stimulation are the hydrolysis of phosphatidylinositol bisphosphate to inositol trisphosphate (Ins P3) and 1,2-diacylglycerol (DAG)5–7, and an increase in the concentration of intracellular Ca2+ ([Ca2+]i)8–11. Later, the cell secretes lymphokines and expresses lymphokine receptors1. It has been postulated that the products of the hydrolysis of phosphatidylinositols (Ptd Ins) and fluctuations in [Ca2+]i are critical 'second messengers≈, transmitting the signals for the initiation of the later events. We have examined the relationship between these second messengers and the secretion of IL-2 in a murine T cell variant whose missing TCR complex had been reconstituted by gene transfer. Surprisingly, although the IL-2 responses of the transfectant could not be distinguished from the original line expressing the same TCR, Ptd Ins hydrolysis and the increase in [Ca2+]i were substantially reduced or absent in the reconstituted cell. It is therefore possible to dissociate these early biochemical changes from a late biological response, raising questions about the putative causal relationship of these events.