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Blood, 1 September 2001, Vol. 98, No. 5, pp. 1512-1523
IMMUNOBIOLOGY
Cytokine production by mouse myeloid dendritic cells in relation
to differentiation and terminal maturation induced by
lipopolysaccharide or CD40 ligation
Adrian E. Morelli,
Alan F. Zahorchak,
Adriana T. Larregina,
Bridget L. Colvin,
Alison J. Logar,
Takuya Takayama,
Louis D. Falo, and
Angus W. Thomson
From the Thomas E. Starzl Transplantation Institute and
the Departments of Surgery, Molecular Genetics and Biochemistry, and
Dermatology, and the University of Pittsburgh Cancer Institute,
University of Pittsburgh Medical Center, PA.
Although it is known that dendritic cells (DCs) produce cytokines,
there is little information about how cytokine synthesis is regulated
during DC development. A range of cytokine mRNA/proteins was analyzed
in immature (CD86 ) or mature (CD86+) murine
bone marrow (BM)- derived DCs. Highly purified, flow-sorted, immature
DCs exhibited higher amounts of interleukin-1 (IL-1 ), IL-1 ,
tumor necrosis factor- (TNF- ), transforming growth factor 1
(TGF- 1), and macrophage migration inhibitory factor (MIF) mRNA/protein than mature DCs. After differentiation, DC up-regulated the levels of IL-6 and IL-15 mRNA/protein and synthesized de novo mRNA/protein for IL-12p35, IL-12p40, and IL-18. Although immature BM-derived DCs did not stimulate naive allogeneic T cells, mature DCs
elicited a mixed population of T helper (Th) 1 (mainly) and Th2 cells
in 3d-mixed leukocyte reactions. CD86+ BM DCs switched to
different cytokine patterns according to whether they were terminally
differentiated by lipopolysaccharide (LPS) or CD40 ligation. Although
both stimuli increased IL-6, IL-12p40, IL-15, and TNF- mRNA/protein
levels, only LPS up-regulated transcription of IL-1 , IL-1 ,
IL-12p35, and MIF genes. Although LPS and CD40 cross-linking increased
the T-cell allostimulatory function of BM DCs, only LPS stimulation
shifted the balance of naive Th differentiation to Th1 cells, a
mechanism dependent on the up-regulation of IL-12p35 and not of IL-23.
These results demonstrate that, depending on the stimuli used to
terminally mature BM DCs, DCs synthesize a different pattern of
cytokines and exhibit distinct Th cell-driving potential.

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M. Menges, S. Ro{beta}ner, C. Voigtlander, H. Schindler, N. A. Kukutsch, C. Bogdan, K. Erb, G. Schuler, and M. B. Lutz
Repetitive Injections of Dendritic Cells Matured with Tumor Necrosis Factor {alpha} Induce Antigen-specific Protection of Mice from Autoimmunity
J. Exp. Med.,
December 31, 2001;
195(1):
15 - 22.
[Abstract]
[Full Text]
[PDF]
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