Shih C C, Bollom M
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Cell Immunol. 1990 Oct 1;130(1):160-75. doi: 10.1016/0008-8749(90)90170-v.
The class II MHC antigen-specific CTL clones described in this report lose lytic activity when grown in exogenous rIL-2, but regain lytic activity when rIL-2 is removed from the culture medium. Using this cell model, we have investigated the metabolic activities (i.e., DNA, RNA, and protein synthesis) required for CTL to acquire or down-regulate lytic activity. DNA synthesis inhibitors (hydroxyurea and cytosine-arabinoside) and irradiation did not prevent CTL from gaining lytic activity. However, when protein or RNA synthesis was inhibited, these CTL could no longer acquire lytic activity. Furthermore, evidence showed that continuous RNA and protein syntheses were essential for CTL to exert their lytic function. Studies on cell surface antigen expression of CD3, CD4, Thy-1, and LFA-1 revealed no significant difference of antigen expression between a cloned CTL in its lytic and nonlytic states. Our data suggested that the synthesis of certain proteins and their encoded mRNA are essential for CTL to exert its lytic function and these proteins are not the cell surface antigens involved in CTL-target recognition or binding. Data also indicated that a granule enzyme, serine-esterase, was not involved in the expression of lytic activity in these CTL clones.
本报告中描述的II类MHC抗原特异性CTL克隆在含有外源性rIL-2的条件下培养时会丧失裂解活性，但当从培养基中去除rIL-2时又会恢复裂解活性。利用这个细胞模型，我们研究了CTL获得或下调裂解活性所需的代谢活性（即DNA、RNA和蛋白质合成）。DNA合成抑制剂（羟基脲和阿糖胞苷）以及辐射并未阻止CTL获得裂解活性。然而，当蛋白质或RNA合成受到抑制时，这些CTL就不再能够获得裂解活性。此外，有证据表明，持续的RNA和蛋白质合成对于CTL发挥其裂解功能至关重要。对CD3、CD4、Thy-1和LFA-1细胞表面抗原表达的研究表明，克隆的CTL在其裂解状态和非裂解状态下，抗原表达没有显著差异。我们的数据表明，某些蛋白质及其编码的mRNA的合成对于CTL发挥其裂解功能至关重要，并且这些蛋白质不是参与CTL-靶细胞识别或结合的细胞表面抗原。数据还表明，颗粒酶丝氨酸酯酶不参与这些CTL克隆中裂解活性的表达。
