Polyethylene glycol-modified GM-CSF expands CD11b(high)CD11c(high) but notCD11b(low)CD11c(high) murine dendritic cells in vivo: a comparative analysis with Flt3 ligand.
Dendritic cells (DC) are potent APCs that can be characterized in the murine spleen as CD11b(high)CD11c(high) or CD11b(low)CD11c(high). Daily injection of mice of Flt3 ligand (FL) into mice transiently expands both subsets of DC in vivo, but the effect of administration of GM-CSF on the expansion of DC in vivo is not well defined. To gain further insight into the role of GM-CSF in DC development and function in vivo, we treated mice with polyethylene glycol-modified GM-CSF (pGM-CSF) which has an increased half-life in vivo. Administration of pGM-CSF to mice for 5 days led to a 5- to 10-fold expansion of CD11b(high)CD11c(high) but not CD11b(low)CD11c(high) DC. DC from pGM-CSF-treated mice captured and processed Ag more efficiently than DC from FL-treated mice. Although both FL- and pGM-CSF-generated CD11b(high)CD11c(high) DC were CD8alpha-, a greater proportion of these DC from pGM-CSF-treated mice were 33D1+ than from FL-treated mice. CD11b(low)CD11c(high) DC from FL-treated mice expressed high levels of intracellular MHC class II. DC from both pGM-CSF- and FL-treated mice expressed high levels of surface class II, low levels of the costimulatory molecules CD40, CD80, and CD86 and were equally efficient at stimulating allogeneic and Ag-specific T cell proliferation in vitro. The data demonstrate that treatment with pGM-CSF in vivo preferentially expands CD11b(high)CD11c(high) DC that share phenotypic and functional characteristics with FL-generated CD11b(high)CD11c(high) DC but can be distinguished from FL-generated DC on the basis of Ag capture and surface expression of 33D1.
Daro
E
E
Department of Immunobiology, Research Administration, and Analytical Chemistry and Formulation, Immunex Corporation, Seattle, WA 98101, USA.
Pulendran
B
B
Brasel
K
K
Teepe
M
M
Pettit
D
D
Lynch
D H
DH
Vremec
D
D
Robb
L
L
Shortman
K
K
McKenna
H J
HJ
Maliszewski
C R
CR
Maraskovsky
E
E
D000818:Animals; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000096:biosynthesis; D015415:Biomarkers; D019013:CD40 Antigens / Q000096:biosynthesis; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D003911:Dextrans / Q000276:immunology / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006410:Hematopoiesis / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007275:Injections, Intravenous; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000008:administration & dosage / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D018122:B7-1 Antigen; D015415:Biomarkers; D019013:CD40 Antigens; D003911:Dextrans; D000949:Histocompatibility Antigens Class II; D016167:Integrin alphaXbeta2; D008024:Ligands; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; C084881:flt3 ligand protein; D011092:Polyethylene Glycols; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin