Effects of administration of progenipoietin 1, Flt-3 ligand, granulocyte colony-stimulating factor, and pegylated granulocyte-macrophage colony-stimulating factor on dendritic cell subsets in mice.
We studied the effects of administration of several cytokines, including progenipoietin-1 (ProGP-1), Flt-3 ligand (FL), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor in a pegylated form (pGM-CSF), on dendritic cell (DC) populations in mouse spleen. ProGP-1 produced the most striking increase in overall DC numbers, apparently more than its constituent FL and G-CSF components. However, the expansion in DC numbers was strongly subpopulation selective, with ProGP-1 and FL producing selective expansion of CD8+ DCs, whereas pGM-CSF produced selective expansion of CD8- DCs. Surprising differences were observed between the effects of murine and human recombinant FL preparations on murine DCs. Many of the biologic functions of the DC subpopulations expanded by cytokines remained intact, including the capacity of the ProGP-1- and FL-expanded CD8+ DCs to produce the T-helper-1-biasing cytokine interleukin 12 (IL-12). However, the expanded DCs from all but G-CSF-treated mice were deficient in the ability to make interferon gamma, and the CD8+ DCs produced with pGM-CSF treatment had an abrogated capacity to form bioactive IL-12. Such selective expansion of DC populations and alterations in their cytokine-secretion capacity have implications for clinical use of the studied cytokines in immune modulation.
O'Keeffe
Meredith
M
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria 3050, Australia.
Hochrein
Hubertus
H
Vremec
David
D
Pooley
Joanne
J
Evans
Robert
R
Woulfe
Susan
S
Shortman
Ken
K
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016827:CD8 Antigens; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D016827:CD8 Antigens; D003115:Colony-Stimulating Factors; D016207:Cytokines; D008565:Membrane Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein; C434603:progenipoietin-1; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D011092:Polyethylene Glycols; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor