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

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.