用白细胞介素-2基因转染的白细胞介素-2依赖辅助性T细胞的自分泌生长和致瘤性
Autocrine growth and tumorigenicity of interleukin 2-dependent helper T cells transfected with IL-2 gene.
作者信息
Karasuyama H, Tohyama N, Tada T
机构信息
Department of Immunology, Faculty of Medicine, University of Tokyo, Japan.
出版信息
J Exp Med. 1989 Jan 1;169(1):13-25. doi: 10.1084/jem.169.1.13.
Abstract
We introduced a mouse IL-2 cDNA expression vector into an IL-2-dependent mouse helper T cell line HT-2. Transfected cells secreted substantial amounts of IL-2, to which they themselves responded by proliferating without further requirement for exogenous IL-2. The proliferation was a direct function of the cell density and was inhibitable by antibodies against IL-2 or IL-2-R, indicating the autocrine nature of the proliferation. Those producing higher amounts of IL-2 were found to be tumorigenic when inoculated into nude mice. The latency period of tumor development correlated inversely with the level of IL-2 secreted. Tumor cells proliferated in vitro in an IL-2 autocrine fashion indistinguishable from that of the inoculated cells. We thus provide evidence that the aberrant activation of the IL-2 autocrine circuit can lead T cells to malignant transformation.
摘要
我们将小鼠白细胞介素-2（IL-2）cDNA表达载体导入依赖IL-2的小鼠辅助性T细胞系HT-2。转染后的细胞分泌大量IL-2，它们自身对IL-2作出反应，通过增殖而不再需要外源性IL-2。增殖是细胞密度的直接函数，并且可被抗IL-2或IL-2受体的抗体所抑制，这表明增殖具有自分泌性质。当接种到裸鼠体内时，那些产生较高量IL-2的细胞被发现具有致瘤性。肿瘤发生的潜伏期与分泌的IL-2水平呈负相关。肿瘤细胞在体外以与接种细胞无法区分的IL-2自分泌方式增殖。因此，我们提供了证据表明IL-2自分泌回路的异常激活可导致T细胞发生恶性转化。
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