MacLennan I C, Golstein P
J Immunol. 1978 Dec;121(6):2542-6.
Most studies of recognition events in cell-mediated cytolysis have analyzed the conditions that are required to establish mechanically stable binding between effector cells and target cells. This approach has shown that cytolytic T cells require a temperature above 20 degrees C and free divalent cations to bind specifically to target cells. K cells on the other hand were shown to bind to IgG on target cells in the absence of divalent cations at 4 degrees C. In this paper we show that both K cell- and T cell-mediated cytolysis are inhibited by cytochalasin A, if this drug is added to cultures before the effector and target cells have interacted. However, the drug does not block the calcium-dependent lethal hit stage of cytolysis in either system. We then show that in both T cell- and K cell-mediated cytolysis, the cytochalasin A-inhibitable stage can proceed in the absence of divalent cations. We conclude from these data that: 1) both K cell- and T cell-mediated cytolysis have a divalent cation-independent stage, which is inhibitable by cytochalasin A; 2) firm mechanical binding of T effectors to target cells requires divalent cations. It is uncertain if the latter is necessary for cytolysis of whether K cells also have to go through a divalent cation phase before the lethal hit stage. The implications of these findings are discussed, especially as to the possibility that strong binding may not be necessary for T cell-mediated cytolysis.
大多数关于细胞介导的细胞溶解中识别事件的研究,都分析了效应细胞与靶细胞之间建立机械稳定结合所需的条件。这种方法表明,细胞毒性T细胞需要高于20摄氏度的温度和游离二价阳离子才能特异性结合靶细胞。另一方面,已证明K细胞在4摄氏度、无二价阳离子的情况下能与靶细胞上的IgG结合。在本文中我们表明,如果在效应细胞和靶细胞相互作用之前将细胞松弛素A添加到培养物中,K细胞和T细胞介导的细胞溶解都会受到抑制。然而,该药物在这两种系统中均不阻断细胞溶解的钙依赖性致死阶段。然后我们表明,在T细胞和K细胞介导的细胞溶解中,细胞松弛素A可抑制的阶段在无二价阳离子的情况下也能进行。我们从这些数据得出以下结论:1)K细胞和T细胞介导的细胞溶解都有一个不依赖二价阳离子的阶段,该阶段可被细胞松弛素A抑制;2)T效应细胞与靶细胞的牢固机械结合需要二价阳离子。对于细胞溶解而言,后者是否必要以及K细胞在致死阶段之前是否也必须经历一个二价阳离子阶段尚不确定。我们讨论了这些发现的意义,特别是关于T细胞介导的细胞溶解可能不需要强结合的可能性。