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Blood, 15 November 2000, Vol. 96, No. 10, pp. 3499-3504
IMMUNOBIOLOGY
A subset of human monocyte-derived dendritic cells expresses high
levels of interleukin-12 in response to combined CD40
ligand and interferon- treatment
Paul J. Mosca,
Amy C. Hobeika,
Timothy M. Clay,
Smita K. Nair,
Elaine K. Thomas,
Michael A. Morse, and
H. Kim Lyerly
From the Departments of General and Thoracic Surgery,
Pathology, Immunology, and Internal Medicine, Center for Genetic and
Cellular Therapies, Duke University Medical Center, Durham, NC; and
Immunex Inc, Seattle, WA.
Dendritic cells (DCs) may arise from multiple lineages and progress
through a series of intermediate stages until fully mature, at which
time they are capable of optimal antigen presentation and T-cell
activation. High cell surface expression of CD83 is presumed to
correlate with full maturation of DCs, and a number of agents have been
shown to increase CD83 expression on DCs. We hypothesized that
interleukin 12 (IL-12) expression would be a more accurate marker of
functionally mature DCs capable of activating antigen-specific T cells.
We used combinations of signaling through CD40, using CD40 ligand
trimer (CD40L), and interferon gamma to demonstrate that CD83
expression is necessary but not sufficient for optimal production of
IL-12 by DCs. Phenotypically mature DCs could be induced to produce
high levels of IL-12 p70 only when provided 2 simultaneous stimulatory
signals. By intracellular cytokine detection, we determined that only a
subset of cells that express high levels of CD80 and CD83 generate
large amounts of IL-12. DCs matured with both signals are superior to
DCs stimulated with the individual agents in activating
antigen-specific T cell in vitro. These findings have important
implications regarding the identification, characterization, and
clinical application of functionally mature DCs.
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