Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Whereas multiple growth-promoting cytokines have been demonstrated to be involved in regulation of the hemopoietic stem cell (HSC) pool, the potential role of negative regulators is less clear. However, IFN-gamma, if overexpressed, can mediate bone marrow suppression and has been directly implicated in a number of bone marrow failure syndromes, including graft-vs-host disease. Whether IFN-gamma might directly affect the function of repopulating HSCs has, however, not been investigated. In the present study, we used in vitro conditions promoting self-renewing divisions of human HSCs to investigate the effect of IFN-gamma on HSC maintenance and function. Although purified cord blood CD34(+)CD38(-) cells underwent cell divisions in the presence of IFN-gamma, cycling HSCs exposed to IFN-gamma in vitro were severely compromised in their ability to reconstitute long-term cultures in vitro and multilineage engraft NOD-SCID mice in vivo (>90% reduced activity in both HSC assays). In vitro studies suggested that IFN-gamma accelerated differentiation of targeted human stem and progenitor cells. These results demonstrate that IFN-gamma can negatively affect human HSC self-renewal.

Original publication

DOI

10.4049/jimmunol.174.2.752

Type

Journal article

Journal

J Immunol

Publication Date

15/01/2005

Volume

174

Pages

752 - 757

Keywords

ADP-ribosyl Cyclase, ADP-ribosyl Cyclase 1, Animals, Antigens, CD, Antigens, CD34, Cell Differentiation, Cell Lineage, Cells, Cultured, Clone Cells, Dose-Response Relationship, Immunologic, Fetal Blood, Growth Inhibitors, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Humans, Immunophenotyping, Interferon-gamma, Membrane Glycoproteins, Mice, Mice, Inbred NOD, Mice, SCID