Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis

J Exp Med. 2004 Oct 4;200(7):825-34. doi: 10.1084/jem.20041389. Epub 2004 Sep 27.

Abstract

The high affinity interleukin (IL)-15 receptor, IL-15Ralpha, is essential for supporting lymphoid homeostasis. To assess whether IL-15Ralpha's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Ralpha- and IL-2/15Rbeta-deficient mice. We find that IL-15Ralpha-competent, IL-2/15Rbeta-deficient cells are able to support IL-15Ralpha-deficient natural killer (NK) and memory CD8+ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Ralpha-mediated presentation of IL-15 in trans is the primary mechanism by which IL-15Ralpha functions in vivo. Surprisingly, using IL-15- and IL-15Ralpha-deficient mixed chimera, we also find that IL-15 and IL-15Ralpha must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Ralpha is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15Ralpha defines homeostatic niches for NK and memory CD8+ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8+ memory T cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells
  • CD8-Positive T-Lymphocytes / immunology*
  • Flow Cytometry
  • Homeostasis / immunology*
  • Immunologic Memory / immunology
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Radiation Chimera
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism*

Substances

  • Il15ra protein, mouse
  • Interleukin-15
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2