Immune-mediated bone marrow failure in C57BL/6 mice.
Immune-mediated bone marrow failure in C57BL/6 mice.
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DOI：
10.1016/j.exphem.2014.12.006
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发表时间：
2015-04
影响因子：
2.6
通讯作者：
Young, Neal S.
中科院分区：
文献类型：
--
作者：
Chen, Jichun;Desierto, Marie J.;Feng, Xingmin;Biancotto, Angelique;Young, Neal S.
采用6.5戈伊全身照射（TBI）后输注FVB/N（FVB）供体淋巴结（LN）细胞（4-10 × 106/受体）的方法，建立了免疫介导的C57 BL/6（B6）小鼠骨髓衰竭模型。43%的动物死亡，在LN细胞输注后8至14天，存活的动物显示血液中性粒细胞、红细胞、血小板和总BM细胞显著下降。将TBI剂量降低至5Gys或将LN来源从FVB改变为BALB/cBy供体未能产生BM破坏。受影响的动物在血液和BM中显示出显著的CD 8 T淋巴细胞扩增和活化;细胞毒性T细胞具有升高的Fas配体表达，并且是寡克隆的，主要展示Vβ7和Vβ17 T细胞受体。受影响动物的血浆干扰素γ和组织坏死因子α显著增加。趋化因子配体CCL 3、CCL 4、CCL 5、CCL 20、CXCL 2、CXCL 5和造血生长因子G-CSF、M-CSF、GM-CSF、VEGF也升高。在携带Fas基因敲除的B6小鼠中，当它们输注FVB LN细胞时，BM衰竭减轻。我们的模型建立了一个有用的平台，以确定在免疫介导的BM失败的个别基因及其产品的作用。
We established a model of immune-mediated bone marrow (BM) failure in C57BL/6 (B6) mice with 6.5 Gy total body irradiation (TBI) followed by the infusion of 4–10 × 106 lymph node (LN) cells/recipient from FVB/N (FVB) donors. Forty-three percent 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 TBI dose to 5 Gys 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 gamma and tissue necrosis factor alpha in affected animals. Chemokine ligands CCL3, CCL4, CCL5, CCL20, CXCL2, CXCL5 and hematopoietic growth factors G-CSF, M-CSF, GM-CSF, VEGF were also elevated. In B6 mice carrying Fas gene knockout, 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.
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影响因子：
6.5
作者：
Scheinberg, P;Nunez, O;Young, NS
通讯作者：
Young, NS
影响因子：
4.4
作者：
Chen, Jichun;Ellison, Felicia M.;Young, Neal S.
通讯作者：
Young, Neal S.
影响因子：
20.3
作者：
Risitano, AM;Kook, H;Maciejewski, JP
通讯作者：
Maciejewski, JP
影响因子：
6.5
作者：
BARNES, DWH;MOLE, RH
通讯作者：
MOLE, RH
影响因子：
20.3
作者：
Chen, J;Lipovsky, K;Young, NS
通讯作者：
Young, NS