Abstract
Dendritic cells (DC) as potent antigen presenting cells play a pivotal role in the induction and elicitation of allergie immune responses. Due to their high antigen presenting capacity they may also be useful tools for the antigen/allergen-specific modification of immune responses on the T cell level. Recently developed culturing techniques of peripheral blood leukocytes make DC available in higher amounts and allow distinct manipulations of their function.
For the experiments presented below we obtained immature DC with high phagocytotic activity after cultivation of CD14+ monocytes with GM-CSF and IL-4 for uptake of allergens added to the cultures on day 7. For full maturation leading to high antigen presenting capacity DC were incubated with TNF-α, IL-iβ and PGE2 in the presence of varying modifiers described below for additional 2 days. Finally DC were cocultured with autologous T cells from atopic donors with relevant sensitizations to the allergens used in vitro (birch pollen, grass pollen and/or house dust mite) or control donors.
In naive and memory T cells allergen-loaded, but not control DC were able to induce antigen-specific proliferative responses and cytokine production. Production of Th2 cytokines was much higher in atopic donors than in non-atopic donors, especially concerning IL-4 production. Incubation of DC and T cells on collagen I strongly enhanced the IL-12 production of DC and consecutively the production of the Thi cytokine IFN-γ of T cells in an allergen-specific way, while the production of Th2 cytokines was inhibited. Incubation of DC with hydrocortisone during the last 2 days of their maturation period strongly decreased their ability to induce the production of Thi, but not of TI12 cytokines, partially due to a decreased IL-12 secretion of DC combined with the inhibition of the expression of HLA-DR and costimulatory molecules, especially CD86. This inhibition was even stronger when the DC were matured in the presence of IL-10 leading to an inhibition of induction of Thi as well as TI12 cytokine production in autologous T cells from sensitized atopic donors. These T cells could not be stimulated to produce Thi or TI12 cytokines even when they were restimulated with regularly matured allergen-loaded DC. Only the addition of compounds known to be able to break anergy of T cells, like IL-2,were able to restore the responsiveness of the allergen-specific T cells. Enhancement of apoptosis of T cells was not observed after stimulation with IL-io-treatedDC.
These data indicate that DC loaded with allergens depending on their culture conditions are able to deviate an already established allergie immune response from a TI12- to a Thi-dominated response and to induce anergy in allergen-specific Thi and TI12 cells in vitro.
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Saloga, J., Bellinghausen, I., Brand, U., Steinbrink, K., Enk, A.H., Knop, J. (2002). Dendritic Cells and Tolerance. In: Ring, J., Behrendt, H. (eds) New Trends in Allergy V. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55994-5_12
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DOI: https://doi.org/10.1007/978-3-642-55994-5_12
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