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

J Immunol. 2004 Dec 1;173(11):6537-41. doi: 10.4049/jimmunol.173.11.6537.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • Epitopes, T-Lymphocyte
  • Il15ra protein, mouse
  • Interleukin-15
  • Protein Subunits
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2