Cutting edge: transpresentation of IL-15 by bone marrow-derived cells necessitates expression of IL-15 and IL-15R alpha by the same cells.
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.
Sandau
Michelle M
MM
Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Schluns
Kimberly S
KS
Lefrancois
Leo
L
Jameson
Stephen C
SC
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D021122:Protein Subunits / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
D018984:Epitopes, T-Lymphocyte; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2