Autocrine growth and tumorigenicity of interleukin 2-dependent helper T cells transfected with IL-2 gene.
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.
Karasuyama
H
H
Department of Immunology, Faculty of Medicine, University of Tokyo, Japan.
Tohyama
N
N
Tada
T
T
D000818:Animals; D000937:Antigen-Antibody Reactions; D015152:Blotting, Northern; D002455:Cell Division; D004247:DNA / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D014162:Transfection
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D004247:DNA