title: Cytotoxic CD8+ T cells stimulate hematopoietic progenitors by promoting cytokine release from bone marrow mesenchymal stromal cells.
abstract: 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.
authors.affiliation: Tumor Immunology, Department of Clinical Research, University of Bern, 3010 Bern, Switzerland; Institute of Pathology, University of Bern, 3010 Bern, Switzerland.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Schürch
authors.affiliation: Tumor Immunology, Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Riether
authors.affiliation: Tumor Immunology, Department of Clinical Research, University of Bern, 3010 Bern, Switzerland; Department of Medical Oncology, Inselspital, Bern University Hospital and University of Bern, 3010 Bern, Switzerland. Electronic address: adrian.ochsenbein@insel.ch.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Ochsenbein
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000821:virology; D007371:Interferon-gamma / Q000494:pharmacology; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000821:virology; D038042:Myelopoiesis / Q000502:physiology*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D016207:Cytokines; D007371:Interferon-gamma