IL-2 promoter-driven lacZ expression as a monitoring tool for IL-2 expression in primary T cells of transgenic mice

Abstract

A transgenic mouse system has been established to follow the pattern of IL-2 expression at the level of single T cells. This was achieved by introducing a human IL-2 promoter-driven reporter gene (Escherfchla coll lacZ) into the germllne of mice and monitoring Its product, β-galactosldase (β-gal), by FACS analysis. Ex vivo experiments confirmed that the regulated expression of the transgene Is comparable with that of the endogenous IL-2 gene. Transgene expression is induclble by mltogens, restricted to T cells, and diminished by Immunosuppressive agents, such as cyclosporln A, at concentrations known to suppress IL-2 transcription. Depending on the mltogens used, 30–50% of peripheral T cells produced IL-2 with an asynchronous induction pattern, as measured by transgenic β-gal activity. Both helper (CD4⁺CD8⁻) and cytotoxlc T cells (CD4⁻CD8⁺) respond with comparable heterogeneous expression levels but they show different frequencies of β-gal production. Transgenic β-gal-produclng T cells were detectable as early as 2 h after mitogen stimulation. These cells represent a transitional IL-2 secreting, IL-2 receptor α-chaJn negative T cell population, which occurs in the aftocrine process of T cell activation. Administration of staphytococcal enterotoxln A (SEA), a bacterial superantlgen, resulted in a T cell specific (Thy-1.2) increase (2.5-fold) of reporter gene expression in vivo. In summary, we could demonstrate that IL-2 promoter-driven reporter gene expression in transgenic mice is a sensitive tool to characterize IL-2 expressing cells phenotyplcally. With this new mouse model, It Is hoped to better define the role of IL-2 expression in the activation process of defined anttgenlc responses and in the genesis of experimental or genetic disease models.