Publication Date:
2015-12-04
Description:
Interferon gamma (IFN-) has been reported to have both negative and positive activity on hematopoietic cells, adding complexity to the interpretation of its pleiotropic functions. We examined the effects of IFN- on murine hematopoietic stem cells (HSCs) and progenitors in vitro and in vivo by using mouse models. IFN- treatment expanded bone marrow (BM) c-Kit + Sca1 + Lin – (KSL) cell number but reduced BM KLCD150 + and KLCD150 + CD48 – cells. IFN--expanded KSL cells engrafted poorly when tested by competitive repopulation in vivo. KSL, KLCD150 + , and KLCD150 + CD48 – cells from IFN--treated animals all showed significant upregulation in Fas expression. When cocultured with activated T cells in vitro, KSL and KLCD150 + cells from IFN--treated donors showed increased apoptosis relative to those from untreated animals, and infusion of activated CD8 T cells into IFN--injected animals in vivo led to partial elimination of KSL cells. Exposure of BM cells or KSL cells to IFN- increased expression of Fas , caspases, and related proapoptotic genes and decreased expression of Ets-1 and other hematopoietic genes. In mouse models of BM failure, mice genetically deficient in IFN- receptor expression showed attenuation of immune-mediated marrow destruction, whereas effector lymphocytes from IFN--deficient donors were much less potent in initiating BM damage. We conclude that the activity of IFN- on murine hematopoiesis is context dependent. IFN--augmented apoptotic gene expression facilitates destruction of HSCs and progenitors in the presence of activated cytotoxic T cells, as occurs in human BM failure.
Keywords:
Hematopoiesis and Stem Cells, Immunobiology, Red Cells, Iron, and Erythropoiesis
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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