Expression of IL-15RA or an IL-15/IL-15RA fusion on CD8+ T cells modifies adoptively transferred T-cell function in cis

Eur J Immunol. 2009 Feb;39(2):491-506. doi: 10.1002/eji.200838594.


IL-15 and IL-15 receptor alpha (IL-15RA) play a significant role in multiple aspects of T-cell biology. However, given the evidence that IL-15RA can present IL-15 in trans, the functional capacity of IL-15RA expressed on CD8(+) T cells to modify IL-15 functions in cis is currently unclear. In the current study, we explore the functional consequences of IL-15RA, expression on T cells using a novel method to transfect naive CD8(+) T cells. We observed that RNA nucleofection led to highly efficient, non-toxic, and rapid manipulation of protein expression levels in unstimulated CD8(+) T cells. We found that transfection of unstimulated CD8(+) T cells with IL-15RA RNA led to enhanced viability of CD8(+) T cells in response to IL-15. Transfection with IL-15RA enhanced IL-15-mediated phosphorylation of STAT5 and also promoted IL-15-mediated proliferation in vivo of adoptively transferred naïve CD8(+) T cells. We demonstrated that IL-15RA can present IL-15 via cis-presentation on CD8(+) T cells. Finally, we showed that transfection with a chimeric construct linking IL-15 to IL-15RA cell autonomously enhances the viability and proliferation of primary CD8(+) T cells and cytotoxic potential of antigen-specific CD8(+) T cells. The clinical implications of the current study are discussed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Proliferation
  • Cell Survival / immunology
  • Interferon-gamma / immunology
  • Interleukin-15 / biosynthesis*
  • Interleukin-15 / genetics
  • Interleukin-15 Receptor alpha Subunit / biosynthesis*
  • Interleukin-15 Receptor alpha Subunit / genetics
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus E7 Proteins / immunology
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • STAT5 Transcription Factor / metabolism
  • Transfection


  • Interleukin-15
  • Interleukin-15 Receptor alpha Subunit
  • Papillomavirus E7 Proteins
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Interferon-gamma