Cytotoxic CD8+ T cells stimulate hematopoietic progenitors by promoting cytokine release from bone marrow mesenchymal stromal cells

Cell Stem Cell. 2014 Apr 3;14(4):460-72. doi: 10.1016/j.stem.2014.01.002. Epub 2014 Feb 20.


Cytotoxic CD8(+) T cells (CTLs) play a major role in host defense against intracellular pathogens, but a complete clearance of pathogens and return to homeostasis requires the regulated interplay of the innate and acquired immune systems. Here, we show that interferon γ (IFNγ) secreted by effector CTLs stimulates hematopoiesis at the level of early multipotent hematopoietic progenitor cells and induces myeloid differentiation. IFNγ did not primarily affect hematopoietic stem or progenitor cells directly. Instead, it promoted the release of hematopoietic cytokines, including interleukin 6 from bone marrow mesenchymal stromal cells (MSCs) in the hematopoietic stem cell niche, which in turn reduced the expression of the transcription factors Runx-1 and Cebpα in early hematopoietic progenitor cells and increased myeloid differentiation. Therefore, our study indicates that, during an acute viral infection, CTLs indirectly modulate early multipotent hematopoietic progenitors via MSCs in order to trigger the temporary activation of emergency myelopoiesis and promote clearance of the infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arenaviridae Infections / immunology
  • Arenaviridae Infections / virology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism*
  • Female
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / virology
  • Interferon-gamma / pharmacology
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / virology
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology
  • Myeloid Cells / virology
  • Myelopoiesis / physiology*
  • Signal Transduction
  • T-Lymphocytes, Cytotoxic / immunology*


  • Cytokines
  • Interferon-gamma