Gray L S, Gnarra J, Hewlett E L, Engelhard V H
Department of Pathology, University of Virginia School of Medicine, Charlottesville 22908.
J Exp Med. 1988 Jun 1;167(6):1963-8. doi: 10.1084/jem.167.6.1963.
Cholera toxin (CT), but not pertussis toxin (PT), treatment of cloned murine CTL inhibited target cell lysis in a dose-dependent fashion. The effects of CT were mimicked by forskolin and cyclic adenosine monophosphate (cAMP) analogues. Inhibition of cytotoxicity by CT and cAMP analogs was mediated in part by attenuation of conjugate formation. Additionally, both CT and cAMP analogs blocked the increase in intracellular Ca2+ induced by stimulation of the TCR complex by mAbs. These findings indicate that cAMP inhibits the activity of CTL by two distinct mechanisms and suggests a role for this second messenger in CTL-mediated cytolysis.
霍乱毒素(CT)而非百日咳毒素(PT)处理克隆的小鼠细胞毒性T淋巴细胞(CTL),会以剂量依赖的方式抑制靶细胞裂解。毛喉素和环磷酸腺苷(cAMP)类似物可模拟CT的作用。CT和cAMP类似物对细胞毒性的抑制部分是通过减弱共轭形成来介导的。此外,CT和cAMP类似物均阻断了单克隆抗体刺激TCR复合物诱导的细胞内Ca2+增加。这些发现表明,cAMP通过两种不同机制抑制CTL的活性,并提示这种第二信使在CTL介导的细胞溶解中发挥作用。