Title
Interleukin-4 and interferon-<tex>$\gamma$</tex> costimulate the expansion of early human myeloid colony-forming cells : proposal of a model for the regulation of myelopoiesis by interleukin 4 and interferon <tex>$\gamma$</tex> and its integration with the regulation of the immune responseInterleukin-4 and interferon-<tex>$\gamma$</tex> costimulate the expansion of early human myeloid colony-forming cells : proposal of a model for the regulation of myelopoiesis by interleukin 4 and interferon <tex>$\gamma$</tex> and its integration with the regulation of the immune response
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Vaccine & Infectious Disease Institute (VAXINFECTIO)
Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO)
Faculteit Geneeskunde
Publication type
article
Publication
Baltimore, Md,
Subject
Human medicine
Source (journal)
Leukemia. - Baltimore, Md, 1987, currens
Volume/pages
10(1996), p. 117-122
ISSN
0887-6924
ISI
A1996TT76000019
Carrier
E
Target language
English (eng)
Affiliation
University of Antwerp
Abstract
We have previously shown that interleukin 4 (IL-4) and interferon gamma (lFN-gamma) reciprocally regulate the production of granulocytes and monocytes from mature monopotential hematopoietic progenitor cells, while at the level of the very primitive stem cells IFN-gamma is a selective inhibitor of proliferation and differentiation, and IL-4 has weak stimulatory effects. We investigated the effects of IL-4 and IFN-gamma on the expansion in suspension culture of myeloid colony-forming cells (CFCs) induced by either IL-3 or IL-1+IL-3, using on the one hand more differentiated CD34+HLA-DR strongly positive (HLA-DR++) and on the other hand more primitive CD34+HLA-DR weakly positive (HLA-DR+/-) human bone marrow cells. It is shown that both IL-4 and IFN-gamma stimulate the IL-3- and IL-3+IL-1-induced expansion of the number of CFCs in the HLA-DR+/- population. In the presence, but not in the absence of IL-1, additive effects of IL-4 and lFN-gamma were seen. We could not demonstrate any IL-3-like effect by IL-4 on early human hematopoietic progenitors. No expansion of CFC number was seen in the HLA-DR++ population. Based on these data and on data which we have published previously, a model for the regulation of myelopoiesis by IL-4 and IFN-gamma is proposed. In this model, IL-4 and IFN-gamma, which are both immune recognition induced inflammatory cytokines, both stimulate the expansion and recruitment of early myeloid progenitors, whereas at the level of their terminal differentiation, the balance between both cytokines determines whether preferentially monocytes/macrophages (IFN-gamma) or granulocytes (IL-4) are being produced. At the level of the most primitive cells, the inhibitory action of IFN-gamma might prevent differentiative exhaustion of the stem cell compartment in situations of hematopoietic stress.
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