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Prepublished online as a Blood First Edition Paper on May 8, 2003; DOI 10.1182/blood-2002-12-3854.
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Blood, 1 September 2003, Vol. 102, No. 5, pp. 1753-1763
IMMUNOBIOLOGY
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
Michael Jefford,
Max Schnurr,
Tracey Toy,
Kelly-Anne Masterman,
Amanda Shin,
Tina Beecroft,
Tsin Yee Tai,
Ken Shortman,
Mark Shackleton,
Ian D. Davis,
Phil Parente,
Thomas Luft,
Weisan Chen,
Jonathan Cebon, and
Eugene Maraskovsky
From the The Melbourne Tumour Biology Branch, Ludwig Institute for Cancer
Research, Austin and Repatriation Medical Centre, Heidelberg, Victoria,
Australia; Medizinische Klinik und Poliklinik V, University of Heidelberg,
Heidelberg, Germany; and The Walter and Eliza Institute of Medical Research,
Parkville, Victoria, Australia.
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- (IFN-) 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.
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