title: Expression of IL-15RA or an IL-15/IL-15RA fusion on CD8+ T cells modifies adoptively transferred T-cell function in cis.
abstract: 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.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Rowley
authors.forename: Archana
authors.initials: A
authors.lastname: Monie
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000235:genetics; D053720:Interleukin-15 Receptor alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014162:Transfection
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D007371:Interferon-gamma