Février M, Foa C, Simonetti J, Prevot C, Barad M, Berebbi M
Br J Exp Pathol. 1987 Apr;68(2):145-56.
This study demonstrates that cytolytic T-cell lines exhibit progressive in-vitro modifications of their phenotype and of their growth behaviour and may use different pathways for their multiplication. Comparing three established cell lines, we firstly demonstrated that the expression of LFA-I is stable but the Lyt 2, 3 is rapidly lost. In this case, a high lectin-dependent cytotoxicity appears. Secondly, we demonstrated that two of the cell lines used the interleukin 2-interleukin 2 receptors (IL-2-IL-2R) binding pathway. Two different monoclonal antibodies showed that the IL-2 receptors distribution does not correlate with the number of functional sites which determines the IL-2 requirement. In contrast, the third cell line, although bearing high levels of IL-2 receptors, grows without the addition of IL-2; this cell growth is not inhibited by anti-IL-2 receptors monoclonal antibodies. Thirdly, it appears that the new property of IL-2 independence is associated with acquisition of the simultaneous capacity to induce tumour grafts in nude mice. As it has been recently reported that cytolytic T-lymphocytes against tumour cells could be promising immunotherapeutic agents, the spontaneous malignant transformation of such CTL lines should be taken into account before using them for adoptive immunotherapeutic purposes.
本研究表明,细胞溶解性T细胞系在体外其表型和生长行为会发生渐进性改变,且可能通过不同途径进行增殖。比较三个已建立的细胞系,我们首先证明淋巴细胞功能相关抗原-1(LFA-I)的表达是稳定的,但Lyt 2、3会迅速丢失。在这种情况下,会出现高凝集素依赖性细胞毒性。其次,我们证明其中两个细胞系利用白细胞介素2-白细胞介素2受体(IL-2-IL-2R)结合途径。两种不同的单克隆抗体表明,IL-2受体的分布与决定IL-2需求的功能位点数量无关。相反,第三个细胞系虽然带有高水平的IL-2受体,但在不添加IL-2的情况下也能生长;这种细胞生长不受抗IL-2受体单克隆抗体的抑制。第三,似乎不依赖IL-2的新特性与获得在裸鼠中诱导肿瘤移植的同时能力有关。由于最近有报道称,针对肿瘤细胞的细胞溶解性T淋巴细胞可能是有前景的免疫治疗剂,因此在将此类细胞毒性T淋巴细胞系用于过继免疫治疗目的之前,应考虑到它们的自发恶性转化。