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Signaling T-cell survival and death by IL-2 and IL-15
Elizabeth Zambricki1, Alana Shigeoka, Hidehiro Kishimoto
1Department of Immunology, The Scripps Research Institute, La Jolla, California, USA.
Abstract:
Interleukin 2 (IL-2) and interleukin 15 (IL-15) bind to common T-cell surface receptors comprised of unique alpha (IL-2R alpha or IL-15R alpha) and shared beta/gamma chain subunits. Ligation of this receptor by IL-2 can lead to apoptosis whereas IL-15 ligation favors cell survival. Our study examined intra-cellular signaling events associated with IL-2- and IL-15-induced apoptosis and survival in human T cells. We found IL-2 and IL-15 could both induce apoptosis and survival; the outcome depended on cytokine concentration. No qualitative differences in Jak/Stat, Ras/MAPK or PI3K/AKT signaling were seen over a wide range of IL-2 and IL-15 concentrations. These findings suggest that, like T-cell receptor signaling, IL-2R beta/gamma chain signaling is regulated, or "tuned," by the concentration of cytokine.
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