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Macrophage- and dendritic-cell-derived interleukin-15 receptor alpha supports homeostasis of distinct CD8+ T cell subsets.

Interleukin-15 receptor alpha (IL-15R alpha) is a pleiotropically expressed molecule that chaperones and trans-presents IL-15 to NK and T cells. To investigate whether IL-15R alpha presented by different cells perform distinct physiological functions, we have generated four lines of mice lacking IL-15R alpha in various cell types. We find that IL-15R alpha expression on macrophages but not dendritic cells (DCs) supports the early transition of antigen specific effector CD8(+) T cells to memory cells. After memory CD8(+) T cell differentiation, IL-15R alpha expression on DCs selectively supports central memory CD8(+) T cells, whereas IL-15R alpha expression on macrophages supports both central and effector memory CD8(+) T cells. By contrast, mice lacking IL-15R alpha on macrophages, DCs, or both, exhibit equivalent defects in NK cell homeostasis and activation. These studies define unique roles for macrophage expression of IL-15R alpha and show that NK cells rely upon distinct IL-15R alpha dependent IL-15 signals than memory CD8(+) T cells. Moreover, they demonstrate the diversity, specification, and geographic restriction of cytokine signals.

Pubmed ID: 19913445

Authors

  • Mortier E
  • Advincula R
  • Kim L
  • Chmura S
  • Barrera J
  • Reizis B
  • Malynn BA
  • Ma A

Journal

Immunity

Publication Data

November 20, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI45860

Mesh Terms

  • Animals
  • Antigens, CD27
  • CD8-Positive T-Lymphocytes
  • Dendritic Cells
  • Gene Deletion
  • Homeostasis
  • Immunologic Memory
  • Interleukin-15 Receptor alpha Subunit
  • Killer Cells, Natural
  • Lymphocyte Activation
  • Macrophages
  • Mice
  • Mice, Transgenic
  • T-Lymphocyte Subsets