Dendritic Cells, Obtained from Peripheral Blood Precursors in the Presence of PGE2, Promote Th2 Responses
In order to investigate the impact of an inflamatory mediator PGE2 on the functions of maturing DC we used an in vitro model of DC generation from peripheral blood monocytes. Addition of PGE, (10−9M–10−6M) to the cultures performed in the presence of GM-CSF and IL-4 did not alter the morphology nor high levels of expression of class II MHC and co-stimulatory molecules on arising DC, although at concentrations above 10−8 M, the acquisition of CD1a was selectively prevented. Control DC and the DC maturing in the presence of PGE2 (PGE,-DC) induced a similar proliferation of naive Th cells. Control DC produced high amounts of IL-12, and only trace amounts of IL-10, whereas PGE2-DC produced no IL-12 and high levels of IL-10, when stimulated after the removal of PGE2. The deficient IL-12 production by PGE2-DC was observed after stimulation both in the absence and in the presence of IFNy, and was not compensated during further 48 h culture in the absence of PGE2. Compared to control DC, PGE2-DC induced development of Th cells secreting elevated amounts of IL-4 and IL-5, from naive precursors. These data indicate that elevated tissue levels of PGE, may promote type 2 Th responses by impairing the ability of locally maturing DC to produce IL-12. Since Th2 responses mediate protection in Thl-related autoimmune disorders, the use of PGE2-DC in immunotherapy of such disorders may be considered.
KeywordsDendritic Cell Atopic Dermatitis Lepromatous Leprosy Similar Proliferation Potent Stimulatory Activity
Unable to display preview. Download preview PDF.
- 1.Kaplan, G., G. Walsh, L.S. Guido, P. Meyn, R.A. Burkhardt, R.M. Abalos, J. Barker, P.A. Frindt, T.T. Fajardo, R. Celona, and Z.A. Cohn. 1992. Novel responses of human skin to intradermal recombinant granulocyte/macrophage colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth and enhanced wound healing. J. Ezp. Med. 175: 1717–1728.CrossRefGoogle Scholar
- 8.Sallusto, F. and A. Lanzavecchia. 1994. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α. J. Exp. Med. 179: 1109–1118.PubMedCrossRefGoogle Scholar
- 10.Kalinski, P., C.M. Hilkens, E.A. Wierenga, T.C. van der Pouw-Kraan, R.A. van Lier, J.D. Bos, M.L. Kapsenberg, and F.G. Snijdewint. 1995. Functional maturation of human naive T helper cells in the absence of accessory cells. Generation of IL-4-producing T helper cells does not require exogenous IL-4. J. Immunol. 154: 3753–3760.PubMedGoogle Scholar