Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction.
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.
Vieira
P L
PL
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
de Jong
E C
EC
Wierenga
E A
EA
Kapsenberg
M L
ML
Kaliński
P
P
D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018664:Interleukin-12; D007371:Interferon-gamma; D015232:Dinoprostone