Signaling T-cell survival and death by IL-2 and IL-15.
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.
Zambricki
Elizabeth
E
Department of Immunology, The Scripps Research Institute, La Jolla, California, USA.
Shigeoka
Alana
A
Kishimoto
Hidehiro
H
Sprent
Jon
J
Burakoff
Steven
S
Carpenter
Charles
C
Milford
Edgar
E
McKay
Dianne
D
D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D019409:Interleukin-15; D007376:Interleukin-2; D015375:Receptors, Interleukin-2