Lefor A T
Department of Surgery, University of Maryland, Baltimore 21201.
J Surg Res. 1991 Oct;51(4):316-23. doi: 10.1016/0022-4804(91)90114-2.
Lymphokine activated killer (LAK) cells selectively recognize and lyse a wide variety of tumor cells, including syngeneic, allogeneic, and xenogeneic cells, by a mechanism which remains unknown. It has been shown that trinitrophenyl modification of human peripheral blood lymphocytes (PBLs) and murine blasts induces sensitivity to lysis by LAK cells. We undertook these studies to examine the effects of trinitrophenyl (TNP) on murine normal cells and tumors. Fresh murine PBLs are resistant to LAK mediated lysis and TNP modification of the cell surface has no effect, in direct contrast to results with human cells. However, the addition of anti-TNP antibody demonstrated lysis of the TNP modified cells by an antibody dependent cellular toxicity mechanism showing that these cells can be lysed by LAK cells. Furthermore, TNP did not induce sensitivity to LAK cell mediated lysis on other normal murine tissues including kidney and bone marrow. The lysis of YAC tumor cells is not inhibited by the addition of TNP modified PBLs. A single cell assay demonstrated no conjugation of LAK effector cells and TNP modified PBLs. LAK cells derived from murine PBLs, as is done in the human, were unable to lyse the TNP modified PBLs, ruling out the origin of the LAK cells as the reason for the different results in humans and mice. These observations represent a difference in the spectrum of target cells lysed by human and murine LAK cells, and also demonstrate a response to TNP modification by fresh murine normal tissues and tumors that differs from that observed with murine blasts.(ABSTRACT TRUNCATED AT 250 WORDS)
淋巴因子激活的杀伤(LAK)细胞通过一种尚不清楚的机制选择性地识别并裂解多种肿瘤细胞,包括同基因、异基因和异种细胞。已表明,人外周血淋巴细胞(PBL)和鼠胚细胞的三硝基苯基修饰可诱导其对LAK细胞裂解的敏感性。我们进行这些研究以检验三硝基苯基(TNP)对鼠正常细胞和肿瘤的影响。新鲜的鼠PBL对LAK介导的裂解具有抗性,细胞表面的TNP修饰没有影响,这与人类细胞的结果形成直接对比。然而,添加抗TNP抗体显示通过抗体依赖性细胞毒性机制可裂解TNP修饰的细胞,表明这些细胞可被LAK细胞裂解。此外,TNP并未诱导包括肾脏和骨髓在内的其他正常鼠组织对LAK细胞介导的裂解产生敏感性。添加TNP修饰的PBL不会抑制YAC肿瘤细胞的裂解。单细胞分析表明LAK效应细胞与TNP修饰的PBL之间没有结合。与人类一样,源自鼠PBL的LAK细胞无法裂解TNP修饰的PBL,排除了LAK细胞来源是人类和小鼠结果不同的原因。这些观察结果表明人类和鼠LAK细胞裂解的靶细胞谱存在差异,也证明了新鲜鼠正常组织和肿瘤对TNP修饰的反应与鼠胚细胞不同。(摘要截短于250字)