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Kali
ski2Academic Medical Center, Department of Cell Biology and Histology, University of Amsterdam, Amsterdam, The Netherlands
Activation of immature dendritic cells (DC) in peripheral tissues
induces their migration to lymph nodes and their maturation into
CD83+ DC, which are able to prime naive T cells. The
inflammatory cytokines IL-1ß and TNF-
induce mature DC, which can
secrete IL-12 and promote the development of Th0/Th1-biased cells. DC
maturation factors with a Th2-promoting function have not been
described. Here we show that PGE2, although it does not
induce final DC maturation by itself, synergizes with IL-1ß and
TNF-, and allows their effectiveness at 100-fold lower
concentrations. While being phenotypically identical with the DC
matured in the presence of high concentrations of IL-1ß and TNF-
alone, DC matured in the additional presence of PGE2 show
impaired IL-12 production and bias naive Th cell development toward the
Th2. The ability of DC to produce IL-12 is also suppressed by IL-10,
which in contrast to PGE2, inhibits their maturation. The
differences in the ability to produce IL-12, established during the
final DC maturation, are stable after the removal of modulatory
factors. Importantly, fully mature DC become unsusceptible to
PGE2 and IL-10. This indicates that the levels of IL-12
production in vivo, in mature DC interacting with Th cells within the
lymph nodes, are mainly predetermined at the stage of immature DC in
peripheral tissues. These data imply that the character of
pathogen-induced local inflammatory reaction can "instruct" local
DC to initiate Th1 or Th2-biased responses.
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C. S. Subauste and M. Wessendarp Human Dendritic Cells Discriminate Between Viable and Killed Toxoplasma gondii Tachyzoites: Dendritic Cell Activation After Infection with Viable Parasites Results in CD28 and CD40 Ligand Signaling That Controls IL-12-Dependent and -Independent T Cell Production of IFN-{gamma} J. Immunol., August 1, 2000; 165(3): 1498 - 1505. [Abstract] [Full Text] [PDF]
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Y. Tada, A. Asahina, K. Nakamura, M. Tomura, H. Fujiwara, and K. Tamaki Granulocyte/Macrophage Colony-Stimulating Factor Inhibits IL-12 production of Mouse Langerhans Cells J. Immunol., May 15, 2000; 164(10): 5113 - 5119. [Abstract] [Full Text] [PDF]
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P. L. Vieira, E. C. de Jong, E. A. Wierenga, M. L. Kapsenberg, and P. Kalinski Development of Th1-Inducing Capacity in Myeloid Dendritic Cells Requires Environmental Instruction J. Immunol., May 1, 2000; 164(9): 4507 - 4512. [Abstract] [Full Text] [PDF]
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P. Kalinski, J. H. N. Schuitemaker, C. M. U. Hilkens, E. A. Wierenga, and M. L. Kapsenberg Final Maturation of Dendritic Cells Is Associated with Impaired Responsiveness to IFN-{gamma} and to Bacterial IL-12 Inducers: Decreased Ability of Mature Dendritic Cells to Produce IL-12 During the Interaction with Th Cells J. Immunol., March 15, 1999; 162(6): 3231 - 3236. [Abstract] [Full Text] [PDF]
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I-C. Ho, J. P. Arm, C. O. Bingham III, A. Choi, K. F. Austen, and L. H. Glimcher A Novel Group of Phospholipase A2s Preferentially Expressed in Type 2 Helper T Cells J. Biol. Chem., May 18, 2001; 276(21): 18321 - 18326. [Abstract] [Full Text] [PDF]
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