| First Author | Saligrama PT | Year | 2014 |
| Journal | Cell Death Differ | Volume | 21 |
| Issue | 6 | Pages | 904-14 |
| PubMed ID | 24510126 | Mgi Jnum | J:229345 |
| Mgi Id | MGI:5751650 | Doi | 10.1038/cdd.2014.10 |
| Citation | Saligrama PT, et al. (2014) IL-15 maintains T-cell survival via S-nitrosylation-mediated inhibition of caspase-3. Cell Death Differ 21(6):904-14 |
| abstractText | Caspase activity is critical for both T-cell survival and death. However, little is known regarding what determines caspase activity in cycling T cells. Interleukin (IL)-2 and IL-15 confer very different susceptibilities to T-cell death. We therefore considered that IL-2 and IL-15 differentially regulate caspase activity to influence T-cell survival. We observed that IL-2-cultured primary murine effector T cells manifested elevated levels of caspase-3 activity compared with IL-15-cultured T cells. T cell receptor (TCR) restimulation further increased caspase activity and induced considerable cell death in IL-2-cultured T cells, but provoked only a minimal increase of caspase activity and cell death in IL-15-cultured T cells. IL-2 sensitization to cell death was caspase-3 mediated. Interestingly, increased active caspase-3 levels with IL-2 were independent of active initiator caspase-8 and caspase-9 that were similar with IL-2 and IL-15. Rather, caspase-3 activity was inhibited by posttranslational S-nitrosylation in IL-15-cultured T cells, but not in the presence of IL-2. This paralleled increased reactive nitrogen and oxygen species with IL-15 and reduced glycolysis. Taken together, these data suggest that the metabolic state conferred by IL-15 inhibits T-cell apoptosis in part by maintaining low levels of active caspase-3 via S-nitrosylation. |
