Zöller M, Douvdevani A, Segal S, Apte R N
Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg.
Int J Cancer. 1992 Feb 1;50(3):450-7. doi: 10.1002/ijc.2910500321.
Oncogene-transformed fibroblasts which expressed IL-1, spontaneously or after activation with conditioned medium (CM) and lipopolysaccharide (LPS), regressed in the syngeneic host. Since regression was significantly influenced by the immune competence of the host (see companion report), we speculated that regression was T-cell-mediated. Frequencies of cytotoxic T-cell precursors (CTLp) were in the same range for activated and non-activated, transformed fibroblasts. Furthermore, it was found that lysability of transformed fibroblasts was not influenced by expression of IL-1. These findings exclude the possibility that regression of CM- and LPS-treated transformed fibroblasts may have been due to the appearance of new, strongly immunogenic epitopes. On the other hand, frequencies of CTL were significantly increased after in vivo immunization with IL-1-expressing as compared to IL-1-non-expressing transformed fibroblasts. The in vivo maturation/expansion of CTL could have been the consequence of activation of helper T cells (TH), transformed fibroblast-associated IL-1 delivering the costimulatory signal. Analysis of frequencies and proliferation rates of TH confirmed this assumption. Both parameters were significantly increased after stimulation with transformed fibroblasts expressing IL-1 in comparison to transformed fibroblasts not expressing IL-1. Furthermore, purified T cells apparently depleted of cells expressing MHC class-II antigens, i.e. antigen-presenting cells, proliferated in the presence of transformed fibroblasts expressing IL-1. Since IL-1 rather than MHC class-II antigen expression was the limiting factor, antigen presentation by IL-1-expressing transformed fibroblasts appears unlikely. Instead, maturation of antigen-presenting cells could well have been initiated by tumor-associated IL-1. We conclude that IL-1 expression of transformed fibroblasts plays an important role in the induction of a T-cell-mediated anti-tumor response. The effect is due to increased efficiency in the activation of helper T cells and may be supported by activation of antigen-presenting cells.
表达白细胞介素 -1（IL -1）的癌基因转化成纤维细胞，无论是自发的，还是在用条件培养基（CM）和脂多糖（LPS）激活后，在同基因宿主体内都会发生消退。由于消退受到宿主免疫能力的显著影响（见配套报告），我们推测消退是由T细胞介导的。对于活化和未活化的转化成纤维细胞，细胞毒性T细胞前体（CTLp）的频率处于相同范围。此外，发现转化成纤维细胞的可裂解性不受IL -1表达的影响。这些发现排除了CM和LPS处理的转化成纤维细胞消退可能是由于出现新的、强免疫原性表位的可能性。另一方面，与不表达IL -1的转化成纤维细胞相比，用表达IL -1的细胞进行体内免疫后，CTL的频率显著增加。CTL在体内的成熟/扩增可能是辅助性T细胞（TH）活化的结果，转化成纤维细胞相关的IL -1传递共刺激信号。对TH频率和增殖率的分析证实了这一假设。与不表达IL -1的转化成纤维细胞相比，用表达IL -1的转化成纤维细胞刺激后，这两个参数均显著增加。此外，明显缺乏表达MHC II类抗原的细胞（即抗原呈递细胞）的纯化T细胞，在存在表达IL -1的转化成纤维细胞时会增殖。由于IL -1而非MHC II类抗原表达是限制因素，表达IL -1的转化成纤维细胞进行抗原呈递似乎不太可能。相反，抗原呈递细胞的成熟很可能是由肿瘤相关的IL -1引发的。我们得出结论，转化成纤维细胞的IL -1表达在诱导T细胞介导的抗肿瘤反应中起重要作用。这种作用是由于辅助性T细胞活化效率的提高，并且可能得到抗原呈递细胞活化的支持。
