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The Journal of Immunology, 2000, 164: 4507-4512.
Copyright © 2000 by The American Association of Immunologists

Development of Th1-Inducing Capacity in Myeloid Dendritic Cells Requires Environmental Instruction1

Pedro L. Vieira*, Esther C. de Jong*,{dagger}, Eddy A. Wierenga*, Martien L. Kapsenberg2,*,{dagger} and Pawel Kalinski2,*

Departments of * Cell Biology and Histology and {dagger} Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Dendritic cells (DC) are key initiators of primary immune responses. Myeloid DC can secrete IL-12, a potent Th1-driving factor, and are often viewed as Th1-promoting APC. Here we show that neither a Th1- nor a Th2-inducing function is an intrinsic attribute of human myeloid DC, but both depend on environmental instruction. Uncommitted immature DC require exposure to IFN-{gamma}, at the moment of induction of their maturation or shortly thereafter, to develop the capacity to produce high levels of IL-12p70 upon subsequent contact with naive Th cells. This effect is specific for IFN-{gamma} and is not shared by other IL-12-inducing factors. Type 1-polarized effector DC, matured in the presence of IFN-{gamma}, induce Th1 responses, in contrast to type 2-polarized DC matured in the presence of PGE2 that induce Th2 responses. Type 1-polarized effector DC are resistant to further modulation, which may facilitate their potential use in immunotherapy.




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