Berke G, Rosen D
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
J Immunol. 1988 Sep 1;141(5):1429-36.
Demonstration of C-like "rings," lytic granules, and the Ca2+-dependent lytic proteins--perforin/cytolysin--thereof, in certain cytocidal lymphocytes has led to the hypothesis of a mechanism of lytic granule-exocytosis and a common terminal lytic step in lymphocyte and C-induced lysis. However, neither cytolytic granules, nor formation of C-like rings during lysis have been detected in mature, highly potent, peritoneal exudate CTL (PEL) derived directly from the site of allograft rejection or in cytocidal hybridomas derived from them (PEL hybridomas). We now report that when stimulated in vitro in the presence of Con A supernatant, as a source of T cell growth factors (TCGF) or rIL-2, small in vivo primed PEL transform into large, dividing cytolytic T cells (PEL blasts) that express the same lytic specificity of the original PEL in short term lytic assays. The PEL blasts, in contrast to PEL, possess massive quantities of lytic granules, and protease (N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester esterase) (BLT-esterase) activity as well as non-specific, cell-mediated cytolytic activity in a long term (4-h) assay. These results suggest that the proposed lytic mechanism involving exocytosis of lytic granules, perforin, and BLT-esterases and the formation of 10 to 20-nm lesions may apply to lysis induced by granule-containing effectors such as large granular lymphocytes and TCGF-dependent CTL lines, such as PEL blasts. However, killing by mature, in vivo primed CTL, such as PEL or their hybridomas, appears to be effected through an alternative, contact-induced, self-destruction process(es) of the target not involving secretory lytic granules or the above lesions. Hence, although the expression of lytic granules and BLT-esterase activities in cytolytic lymphocytes devoid of these components is induced by TCGF, these cellular constituents are not necessary for the expression of CTL-mediated target cell lysis by mature effector cells.
在某些具有细胞毒性的淋巴细胞中发现了类C“环”、溶细胞颗粒及其Ca2+依赖性溶细胞蛋白——穿孔素/溶细胞素，这引发了溶细胞颗粒胞吐作用机制以及淋巴细胞和补体诱导的细胞溶解中共同终末溶细胞步骤的假说。然而，在直接取自同种异体移植排斥部位的成熟、高效能的腹腔渗出细胞毒性T淋巴细胞（PEL）或源自它们的细胞毒性杂交瘤（PEL杂交瘤）中，既未检测到溶细胞颗粒，也未检测到细胞溶解过程中类C环的形成。我们现在报告，当在体外存在作为T细胞生长因子（TCGF）来源的伴刀豆球蛋白A上清液或重组白细胞介素-2的情况下受到刺激时，体内预先致敏的小PEL会转变为大的、正在分裂的溶细胞性T细胞（PEL母细胞），在短期溶细胞试验中，这些细胞表现出与原始PEL相同的溶细胞特异性。与PEL相比，PEL母细胞含有大量的溶细胞颗粒，并具有蛋白酶（N-α-苄氧羰基-L-赖氨酸硫代苄酯酯酶）（BLT酯酶）活性以及在长期（4小时）试验中的非特异性细胞介导的溶细胞活性。这些结果表明，所提出的涉及溶细胞颗粒、穿孔素和BLT酯酶胞吐作用以及10至20纳米损伤形成的溶细胞机制可能适用于由含颗粒效应细胞如大颗粒淋巴细胞和依赖TCGF的细胞毒性T淋巴细胞系（如PEL母细胞）诱导的细胞溶解。然而，成熟的、体内预先致敏的细胞毒性T淋巴细胞（如PEL或其杂交瘤）的杀伤作用似乎是通过靶细胞的另一种接触诱导的自我破坏过程实现的，该过程不涉及分泌性溶细胞颗粒或上述损伤。因此，尽管TCGF可诱导缺乏这些成分的溶细胞性淋巴细胞中溶细胞颗粒和BLT酯酶活性的表达，但这些细胞成分对于成熟效应细胞介导的靶细胞溶解的表达并非必需。
