title: Immune-mediated bone marrow failure in C57BL/6 mice.
abstract: We established a model of immune-mediated bone marrow (BM) failure in C57BL/6 (B6) mice with 6.5 G total-body irradiation followed by the infusion of 4-10 × 10(6) lymph node (LN) cells/recipient from Friend leukemia virus B/N (FVB) donors. Forty-three percent of animals succumbed, with surviving animals showing marked declines in blood neutrophils, red blood cells, platelets and total BM cells at 8 to 14 days following LN cell infusion. Lowering the total-body irradiation dose to 5 G or altering the LN source from FVB to BALB/cBy donors failed to produce BM destruction. Affected animals showed significant expansion and activation of CD8 T lymphocytes in both the blood and BM; cytotoxic T cells had elevated Fas ligand expression and were oligoclonal, mainly displaying Vβ7 and Vβ17 T cell receptors. There were significant increases in blood plasma interferon γ and tissue necrosis factor α in affected animals. Chemokine ligands CCL3, CCL4, CCL5, CCL20, CXCL2, and CXCL5 and hematopoietic growth factors G-CSF, M-CSF, GM-CSF, VEGF were also elevated. In B6 mice carrying a Fas gene mutation, BM failure was attenuated when they were infused with FVB LN cells. Our model establishes a useful platform to define the roles of individual genes and their products in immune-mediated BM failure.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: chenji@nhlbi.nih.gov.
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Desierto
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Angélique
authors.initials: A
authors.lastname: Biancotto
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Center for Human Immunology, Autoimmunity, and Inflammation, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology* / Q000528:radiation effects; D053222:Fas Ligand Protein / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014916:Whole-Body Irradiation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor