REGULATION OF PERFORIN GENE-EXPRESSION IN A T-CELL HYBRID WITH INDUCIBLE CYTOLYTIC ACTIVITY

A mouse X rat T cell hybrid (PC60) that does not require interleukin (IL)-2 for proliferation, was used as a model to study regulation of perforin gene expression. Perforin mRNA is barely detectable in non-induced PC60 cells; however, a 30-fold induction is observed after stimulation with IL-1 alone. Peak perforin mRNA levels were reached after 10 h of induction with IL-1, and these levels were maintained for as long as the stimulus was present. IL-2 by itself has no detectable effect. However, in combination with IL-1 it shows the same induction kinetics as IL-1 alone for the first 10 h, subsequently there is synergism (100-fold induction) between IL-1 and IL-2. The induction response was mainly due to increased transcriptional rates of the perforin gene, and require newly synthesized proteins. The half-life of perforin mRNA in this system is about 5 h. In addition. we confirm the existence of two types of mouse perforin mRNA that differ in their 5' untranslated regions, and show evidence that both mRNA are translated in vivo with similar efficiencies.