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

Meredith O'Keeffe, Hubertus Hochrein, David Vremec, Joanne Pooley, Robert Evans, Susan Woulfe, Ken Shortman

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122 Citations (Scopus)

Abstract

We studied the effects of administration of several cytokines, including progenipoietin-1 (ProGP-1), Fit-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 γ, 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 cytokinesecretion capacity have implications for clinical use of the studied cytokines in immune modulation.

Original languageEnglish
Pages (from-to)2122-2130
Number of pages9
JournalBlood
Volume99
Issue number6
DOIs
Publication statusPublished - 15 Mar 2002
Externally publishedYes

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