Merćep M, Noguchi P D, Ashwell J D
Biological Response Modifiers Program, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1989 Jun 1;142(11):4085-92.
Stimulation of transformed T cells leads to both lymphokine secretion and inhibition of spontaneous growth. Studies performed with an Ag-specific T cell hybridoma demonstrated that growth inhibition is an early (within 1 h) manifestation of activation. Experiment in which extracellular Ca2+ was chelated or in which cyclosporine A was included indicated that activation-associated growth inhibition is a two-step process. The first phase is the establishment of a G1/S cell cycle block; it does not require extracellular Ca2+ and is not prevented by the addition of cyclosporine A. The second phase is cell lysis. It can be detected 4 to 6 h after activation, requires the presence of extracellular Ca2+, and is prevented when stimulation occurs in the presence of cyclosporine A. The observation that both Ca2+ depletion and cyclosporine A prevented IL-2 secretion at all time points indicates that the pathways leading to lymphokine secretion and the G1/S block diverge early in the course of the cellular response, and establish the cell cycle block as a distinct activation event with unique characteristics.
对转化的T细胞进行刺激会导致淋巴因子分泌以及自发生长受到抑制。用抗原特异性T细胞杂交瘤进行的研究表明，生长抑制是激活的早期（1小时内）表现。在细胞外Ca2+被螯合或加入环孢素A的实验表明，激活相关的生长抑制是一个两步过程。第一阶段是建立G1/S细胞周期阻滞；它不需要细胞外Ca2+，并且不会因加入环孢素A而受到阻止。第二阶段是细胞裂解。它可在激活后4至6小时被检测到，需要细胞外Ca2+的存在，并且当在环孢素A存在的情况下进行刺激时会被阻止。在所有时间点Ca2+耗竭和环孢素A均能阻止IL-2分泌这一观察结果表明，导致淋巴因子分泌和G1/S阻滞的途径在细胞反应过程的早期就出现分歧，并将细胞周期阻滞确立为具有独特特征的独特激活事件。
