Induction of granulysin in T cells by common gamma‐chain cytokines IL‐2, IL‐15 and IL‐21

Abstract

Granulysin displays potent anti‐microbial activity against many prevalent pathogens including multi‐drug resistant M. tuberculosis. Granulysin is a constituent of cytotoxic granules within T cells and NK cells and its bactericidal activity is dependent on its co‐expression with perforin. The regulation of granulysin expression in T cells is poorly defined due to the lack of a murine gene homologue. The aim of this project is to define the signals required by human T cells to express granulysin. We found that the common gamma‐chain cytokines, IL‐2, IL‐15 and IL‐21 induced the highest levels of mRNA and protein, of perforin and granulysin in T cells compared to TCR stimulation or mitogen. In response to these cytokines, the kinetics of protein expression differed, with perforin levels peaking at 3 days and granulysin at 5 days. Preliminary results indicate that activation of T cells by both IL‐15 and IL‐21 resulted in the degradation of IkB and a concomitant increase in NF‐kB p65 expression. However, dramatic increases in total STAT5 and p‐STAT5 expression were observed in response to IL‐15, but not IL‐21, and coincided with granulysin and perforin expression. Our data suggest that the induction of granulysin and perforin expression by IL‐15 and IL‐21 may be mediated by activation of different signaling pathways. This research is supported by the Dept. of Microbiology and Immunology, UTMB.