Signaling T-cell survival and death by IL-2 and IL-15

Am J Transplant. 2005 Nov;5(11):2623-31. doi: 10.1111/j.1600-6143.2005.01075.x.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Cell Death / drug effects*
  • Cell Death / immunology
  • Cell Line
  • Cell Survival / drug effects*
  • Cell Survival / immunology
  • Humans
  • Interleukin-15 / pharmacology*
  • Interleukin-2 / pharmacology*
  • Lymphocyte Activation / drug effects
  • Receptors, Interleukin-2 / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Interleukin-15
  • Interleukin-2
  • Receptors, Interleukin-2