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* Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702;
Department of Oncology and Neuroscience, University of Chieti, Chieti, Italy;
Cancer and Developmental Biology Laboratory, SAIC-Frederick, National Cancer Institute-Frederick, MD 21702; and
Dana Farber Cancer Institute, Boston, MA 02115
IL-7 administration to mice was previously reported to increase the mobilization of progenitor cells from marrow to peripheral sites. We now report that IL-7 increases the number of mature myeloid and monocytic cells in spleen and peripheral blood. This effect required T cells, and we show that IL-7 treatment in vivo induced GM-CSF and IL-3 production by T cells with memory phenotype. However, additional myelopoietic cytokines were shown to be involved because mice deficient in both GM-CSF and IL-3 also responded to IL-7 with increased myelopoiesis. Candidate cytokines included IFN-
and Flt3 ligand, which were also produced in response to IL-7. Because IFN--deficient mice also increased myelopoiesis, it was suggested that IL-7 induced production of redundant myelopoietic cytokines. In support of this hypothesis, we found that the supernatant from IL-7-treated, purified T cells contained myelopoietic activity that required a combination of Abs against GM-CSF, IL-3, and anti-Flt3 ligand to achieve maximum neutralization. IL-7 administration increased the number of splenic erythroid cells in either normal, Rag1 or GM-CSF-IL-3-deficient mice, suggesting that IL-7 might directly act on erythroid progenitors. In support of this theory, we detected a percentage of TER-119+ erythroid cells that expressed the IL-7R
-chain and common -chain. Bone marrow cells expressing IL-7R and B220 generated erythroid colonies in vitro in response to IL-7, erythropoietin, and stem cell factor. This study demonstrates that IL-7 can promote nonlymphoid hemopoiesis and production of cytokines active in the host defense system in vivo, supporting its possible clinical utility.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.
2 Address correspondence and reprint requests to Dr. Scott K. Durum, Section of Cytokines and Immunity, National Cancer Institute, Building 560, Room 31-56, Frederick, MD 21702. E-mail address: durum{at}ncifcrf.gov
3 Abbreviations used in this paper: Flt3-L, ligand; rhu, human recombinant; HPRT, hypoxanthine phosphoribosyltransferase; F, forward; R, reverse; SCF, stem cell factor; EPO, erythropoietin; int, intermediate; BFU, burst-forming unit; sup, supernatant.
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