Differential regulation of T-cell growth by IL-2 and IL-15

Blood. 2006 Jul 15;108(2):600-8. doi: 10.1182/blood-2005-12-4827. Epub 2006 Mar 28.

Abstract

Although interleukin 2 (IL-2) and IL-15 signal through the common gamma chain (gammac) and through IL-2 receptor beta-chain (CD122) subunits, they direct distinct physiologic and immunotherapeutic responses in T cells. The present study provides some insight into why IL-2 and IL-15 differentially regulate T-cell function by revealing that these cytokines are strikingly distinct in their ability to control protein synthesis and T-cell mass. IL-2 and IL-15 are shown to be equivalent mitogens for antigen-stimulated CD8(+) T cells but not for equivalent growth factors. Antigen-primed T cells cannot autonomously maintain amino acid incorporation or de novo protein synthesis without exogenous cytokine stimulation. Both IL-2 and IL-15 induce amino acid uptake and protein synthesis in antigen-activated T cells; however, the IL-2 response is strikingly more potent than the IL-15 response. The differential action of IL-2 and IL-15 on amino acid uptake and protein synthesis is explained by temporal differences in signaling induced by these 2 cytokines. Hence, the present results show that cytokines that are equivalent mitogens can have different potency in terms of regulating protein synthesis and cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Interleukin-15 / pharmacology*
  • Interleukin-2 / pharmacology*
  • Mice
  • Mice, Transgenic
  • Mitogens / pharmacology
  • Protein Biosynthesis / drug effects
  • Signal Transduction
  • T-Lymphocytes / cytology*

Substances

  • Interleukin-15
  • Interleukin-2
  • Mitogens