Pasternack M S, Verret C R, Liu M A, Eisen H N
Nature. 1986;322(6081):740-3. doi: 10.1038/322740a0.
The mechanisms that enable cytotoxic T lymphocytes (Tc cells) to destroy target cells are only vaguely understood. However, recent studies have identified in Tc cells and natural killer cells cytoplasmic granules that contain perforin, a cytolytic protein that resembles the ninth component of complement (C9). Antigen-specific lysis of target cells, traditionally ascribed solely to Tc cells, has now also been demonstrated in some T-helper cell (Th cell) lines, referred to here as T helper-killer or Th/c cells. We recently found a novel serine esterase that is present at greatly elevated levels in cloned murine Tc cell lines and one Th/c cell line, but not in two non-cytolytic Th cell lines. These findings suggest that the serine esterase is involved in cytolytic activity and that a variety of effector cells share a common cytolytic mechanism. To explore the role of the serine esterase in this process, we have been studying additional properties of the enzyme in murine T cells. We show here that it is a membrane-associated, disulphide-linked dimer, it has trypsin-like properties but is not a general protease, in density gradient centrifugation it sediments with perforin, it is secreted by Tc cells during their cytolytic attack on target cells, and antiserum to Tc-cell serine esterase reacts with the enzyme in Th/c cells.
细胞毒性T淋巴细胞(Tc细胞)杀伤靶细胞的机制目前尚不清楚。然而,最近的研究发现,Tc细胞和自然杀伤细胞的细胞质颗粒中含有穿孔素,这是一种类似于补体第九成分(C9)的溶细胞蛋白。传统上认为,靶细胞的抗原特异性裂解仅由Tc细胞介导,但现在在一些辅助性T细胞(Th细胞)系中也得到了证实,本文称之为辅助性杀伤T细胞或Th/c细胞。我们最近发现了一种新型丝氨酸酯酶,在克隆的小鼠Tc细胞系和一个Th/c细胞系中,该酶的水平显著升高,而在两个非细胞毒性的Th细胞系中则未检测到。这些发现表明,丝氨酸酯酶参与了细胞溶解活性,并且多种效应细胞共享一种共同的细胞溶解机制。为了探究丝氨酸酯酶在此过程中的作用,我们一直在研究该酶在小鼠T细胞中的其他特性。我们在此表明,它是一种与膜相关的、二硫键连接的二聚体,具有类胰蛋白酶的特性,但不是一种普通的蛋白酶,在密度梯度离心中,它与穿孔素一起沉淀,在Tc细胞对靶细胞进行细胞溶解攻击时,它由Tc细胞分泌,并且针对Tc细胞丝氨酸酯酶的抗血清能与Th/c细胞中的该酶发生反应。