Cutting edge: transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15R alpha by the same cells

• Published in: The Journal of immunology (1950) 2004-12, Vol.173 (11), p.6537-6541
• Main Authors: Sandau, Michelle M, Schluns, Kimberly S, Lefrancois, Leo, Jameson, Stephen C
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cells, Cultured; Cross-Priming - genetics; Epitopes, T-Lymphocyte - immunology; Homeostasis - genetics; Homeostasis - immunology; Immunologic Memory - genetics; Interleukin-15 - biosynthesis; Interleukin-15 - deficiency; Interleukin-15 - genetics; Interleukin-15 - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Killer Cells, Natural - pathology; Lymphopenia - genetics; Lymphopenia - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Models, Immunological; Protein Subunits - biosynthesis; Protein Subunits - deficiency; Protein Subunits - genetics; Radiation Chimera - genetics; Radiation Chimera - immunology; Receptors, Interleukin-15; Receptors, Interleukin-2 - biosynthesis; Receptors, Interleukin-2 - deficiency; Receptors, Interleukin-2 - genetics
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.11.6537

IL-15 is critical for generation of multiple lymphoid subsets. Recent data have demonstrated a unique aspect of responses to IL-15, in that cells bearing the IL-15Ralpha chain can bind soluble IL-15 and "transpresent" the cytokine to other cells, allowing the latter to respond to IL-15. However, it is unclear whether IL-15 is normally secreted and then becomes bound to surface IL-15Ralpha on bystander cells, or whether transpresentation is mediated by the same cells which synthesize IL-15. Using mixed bone marrow chimeric mice, we present evidence for the latter model, showing that development of NK cells and memory phenotype CD8 T cells necessitates that both IL-15 and IL-15Ralpha be expressed by the same population of cells. These data argue that soluble forms of IL-15 are irrelevant for physiological responses to this cytokine, and the implications of this finding are discussed.