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IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells
Open accessAbstract
We studied to what extent the presence of an inflammatory mediator PGE2, during the development of dendritic cells (DC) affects their subsequent ability to induce Th1- and Th2-type cytokines in maturing naive Th cells. PGE2 (10(-9)-10(-6) M) did not alter the morphology or the expression of class II MHC and costimulatory molecules on DC obtained from monocytes in the presence of granulocyte-macrophage CSF and IL-4, although at concentrations above 10(-8) M, PGE2 prevented the acquisition of CD1a marker. Both control DC and DC maturing in the presence of PGE2 (PGE2-DC) were potent stimulators of naive Th cells. In contrast to control DC, which produced high amounts of IL-12 and trace amounts of IL-10, PGE2-DC produced no IL-12 and high amounts of IL-10 when stimulated in the absence of PGE2. This distinct cytokine profile of PGE2-DC was stable for at least 48 h of additional culture in the absence of PGE2. Control DC induced the development of Th0-like cells from superantigen-activated naive Th cells, whereas PGE2-DC promoted the development of Th cells that produced high amounts of IL-4 and IL-5. Experiments using IL-12-neutralizing Abs or rIL-12 indicated a crucial role of IL-12 deficiency in the induction of type 2 cytokine profiles. These findings suggest that elevated levels of PGE2 promote type 2 Th responses by stably impairing the ability of maturing DC to produce IL-12. Since type 2 Th responses are protective in several Th1-related autoimmune disorders, PGE2-DC may be considered for use in immunotherapy.
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Metadata
- Authors
- Kaliński, P., Hilkens, C. M., Snijders, A., Snijdewint, F. G., & Kapsenberg, M. L.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1997-07-01
- Volume
- 159
- Issue
- 1
- Pages
- 28-35
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1568945049
- Cited by
- 602
- References
- 0
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Open access
- green
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