IL-2 PROMOTER-DRIVEN LACZ EXPRESSION AS A MONITORING TOOL FOR IL-2 EXPRESSION IN PRIMARY T-CELLS OF TRANSGENIC MICE

A transgenic mouse system has been established to follow the pattern o f IL-2 expression at the level of single T cells. This was achieved by introducing a human IL-2 promoter-driven reporter gene (Escherichia c oli lacZ) into the germline of mice and monitoring its product, beta-g alactosidase (beta-gal), by FACS analysis. Ex vivo experiments confirm ed that the regulated expression of the transgene is comparable with t hat of the endogenous IL-2 gene. Transgene expression is inducible by mitogens, restricted to T cells, and diminished by immunosuppressive a gents, such as cyclosporin A, at concentrations known to suppress IL-2 transcription. Depending on the mitogens used, 30 - 50% of peripheral T cells produced IL-2 with an asynchronous induction pattern, as meas ured by transgenic beta-gal activity. Both helper (CD4+CD8-) and cytot oxic T cells (CD4-CD8+) respond with comparable heterogeneous expressi on levels but they show different frequencies of beta-gal production. Transgenic beta-gal-producing T cells were detectable as early as 2 h after mitogen stimulation. These cells represent a transitional IL-2 s ecreting, IL-2 receptor alpha-chain negative T cell population, which occurs in the autocrine process of T cell activation. Administration o f staphylococcal enterotoxin A (SEA), a bacterial superantigen, result ed 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 promot er-driven reporter gene expression in transgenic mice is a sensitive t ool to characterize IL-2 expressing cells phenotypically. With this ne w mouse model, it is hoped to better define the role of IL-2 expressio n in the activation process of defined antigenic responses and in the genesis of experimental or genetic disease models.