Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9492
Title: Functional comparison of DCs generated in vivo with Flt3 ligand or in vitro from blood monocytes: differential regulation of function by specific classes of physiologic stimuli.
Authors: Jefford, Michael;Schnurr, Max;Toy, Tracey;Masterman, Kelly-Anne;Shin, Amanda;Beecroft, Tina;Tai, Tsin Yee;Shortman, Ken;Shackleton, Mark;Davis, Ian D;Parente, Phil;Luft, Thomas;Chen, Weisan;Cebon, Jonathan S;Maraskovsky, Eugene
Affiliation: Ludwig Institute Oncology Unit, Austin and Repatriation Medical Centre, Studley Rd, Heidelberg, Victoria 3084, Australia.
Issue Date: 8-May-2003
Citation: Blood 2003; 102(5): 1753-63
Abstract: Dendritic cells (DCs) are a family of leukocytes that initiate T- and B-cell immunity against pathogens. Migration of antigen-loaded DCs from sites of infection into draining lymphoid tissues is fundamental to the priming of T-cell immune responses. In humans, the major peripheral blood DC (PBDC) types, CD1c+ DCs and interleukin 3 receptor-positive (IL-3R+) plasmacytoid DCs, are significantly expanded in vivo with the use of Flt3 ligand (FL). DC-like cells can also be generated from monocyte precursors (MoDCs). A detailed comparison of the functional potential of these types of DCs (in an autologous setting) has yet to be reported. Here, we compared the functional capacity of FL-expanded CD1c+ PBDCs with autologous MoDCs in response to 3 different classes of stimuli: (1) proinflammatory mediators, (2) soluble CD40 ligand trimer (CD40L), and (3) intact bacteria (Escherichia coli). Significant differences in functional capacities were found with respect to changes in phenotype, migratory capacity, cytokine secretion, and T-cell stimulation. MoDCs required specific stimuli for the expression of functions. They responded vigorously to CD40L or E coli, expressing cytokines known to regulate interferon-gamma (IFN-gamma) in T cells (IL-12p70, IL-18, and IL-23), but required prostaglandin E2 (PGE2) during stimulation to migrate to chemokines. In contrast, PBDCs matured in response to minimal stimulation, rapidly acquired migratory function in the absence of PGE2-containing stimuli, and were low cytokine producers. Interestingly, both types of DCs were equivalent with respect to stimulation of allogeneic T-cell proliferation and presentation of peptides to cytotoxic T lymphocyte (CTL) lines. These distinct differences are of particular importance when considering the choice of DC types for clinical applications.
Internal ID Number: 12738673
URI: http://ahro.austin.org.au/austinjspui/handle/1/9492
DOI: 10.1182/blood-2002-12-3854
URL: http://www.ncbi.nlm.nih.gov/pubmed/12738673
Type: Journal Article
Subjects: Antigens, CD1.metabolism
CD40 Ligand.pharmacology
Cell Differentiation.drug effects.immunology
Cell Division.immunology
Cell Movement.immunology
Cells, Cultured
Cytokines.biosynthesis
Dendritic Cells.cytology.immunology.metabolism
Escherichia coli
Glycoproteins.metabolism
Humans
Immunophenotyping
In Vitro Techniques
Inflammation Mediators.pharmacology
Lymphocyte Activation.immunology
Melanoma.immunology
Membrane Proteins.pharmacology
Monocytes.cytology
Peptides.pharmacology
Stimulation, Chemical
T-Lymphocytes.cytology.immunology
Appears in Collections:Journal articles

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