Fas-mediated lysis of target cell by IL-2 treated cytotoxic T lymphocytes

Interleukin-2 (IL-2) plays an important role as an immunoregulatory mediator. It is also known to enhance the killing activity of killer cells such as natural killer (NK) cells or lymphokine-activated killer (LAK) cells. When cytotoxic T lymphocytes (CTL) lyse antigen (Ag)-treated target cells, the presence of IL-2 enhances the killing activity of CTL. In the present study, we examined the mechanisms by which IL-2 treated CTL lyse normal target cells at the cellular and mRNA levels. Our results suggest that IL-2 treated CTL can lyse target cells predominantly via Fas-mediated mechanism and to a lesser extent via a granule exocytosis-based mechanism. Interestingly, the level of FasL mRNA in CTL clone remained unchanged following IL-2 treatment, whereas the level of expression of Fas ligand (FasL) on CTL surface was slightly enhanced. On the other hand, treatment with metalloproteinase inhibitor augmented the level of FasL expression on the cell surface of CTL as well as the activity of target cell killing. Our results indicate that IL-2 plays a crucial role in the regulatory mechanisms of target cell killing by CTL without TCR-stimulation.