IL-7 induces myelopoiesis and erythropoiesis.
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-gamma and Flt3 ligand, which were also produced in response to IL-7. Because IFN-gamma-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-7Ralpha-chain and common gamma-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.
Aiello
Francesca B
FB
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702, USA.
Keller
Jonathan R
JR
Klarmann
Kimberly D
KD
Dranoff
Glenn
G
Mazzucchelli
Renata
R
Durum
Scott K
SK
D000818:Animals; D001773:Blood Cells / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D038042:Myelopoiesis / Q000187:drug effects*; D013154:Spleen / Q000166:cytology
D016207:Cytokines; D007377:Interleukin-3; D015851:Interleukin-7; D008565:Membrane Proteins; C084881:flt3 ligand protein; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor