| First Author | Chen J | Year | 2015 |
| Journal | Exp Hematol | Volume | 43 |
| Issue | 4 | Pages | 256-67 |
| PubMed ID | 25555453 | Mgi Jnum | J:230272 |
| Mgi Id | MGI:5755908 | Doi | 10.1016/j.exphem.2014.12.006 |
| Citation | Chen J, et al. (2015) Immune-mediated bone marrow failure in C57BL/6 mice. Exp Hematol 43(4):256-67 |
| abstractText | 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 x 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 Vbeta7 and Vbeta17 T cell receptors. There were significant increases in blood plasma interferon gamma and tissue necrosis factor alpha 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. |
