TY - JOUR
T1 - 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
AU - O'Keeffe, Meredith
AU - Hochrein, Hubertus
AU - Vremec, David
AU - Pooley, Joanne
AU - Evans, Robert
AU - Woulfe, Susan
AU - Shortman, Ken
PY - 2002/3/15
Y1 - 2002/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037085754&partnerID=8YFLogxK
U2 - 10.1182/blood.V99.6.2122
DO - 10.1182/blood.V99.6.2122
M3 - Article
C2 - 11877288
AN - SCOPUS:0037085754
SN - 0006-4971
VL - 99
SP - 2122
EP - 2130
JO - Blood
JF - Blood
IS - 6
ER -