Co-activation of naive CD4+ T cells and bone marrow-derived mast cells results in the development of Th2 cells |
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Authors: | Huels Christoph; Germann Tieno; Goedert Sigrid; Hoehn Petra; Koelsch Stephan; Hultner Lothar; Palm Norbert; Rude Erwin; Schmitt Edgar |
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Institution: | Institut für Immunologie, University of Mainz 55101 Mainz, Germany
1 GSF—Institut für Experimentelle Hämatologie 81377 München, Germany |
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Abstract: | Activation of nalve dense CD4+ T cells by plate-bound anti-CD3antibodies favors the development of Th1 cells which, upon re-stimulation,produce significant amounts of INF- but no IL-4. However, co-activationof such naive T cells in the presence of IgE anti-dlnitrophenyl(DNP)]-loaded bone marrow-derived mast cells (BMMC) on platescoated with anti-CD3 antibodies and DNP-BSA led to the developmentof IL-4-produclng Th2 cells. The same result could be observedif irradiated (800 rad) BMMC were applied as co-stimulators.Moreover, BMMC could be replaced by the supernatant of IgE-activatedBMMC suggesting that a soluble mediator, presumably IL-4, wasresponsible for this effect. This assumption was substantiatedusing neutralizing anti-IL-4 antibodies which abolished theBMMC-medlated Th2 development in all cases. Addition of IL-12,a cytokine that was shown to antagonize the Th2-promoting effectof IL-4 in vivo, could not inhibit the development of IL-4-producingT cells, but gave rise to a T cell population which producedrelatively high amounts of IL-4 and IFN- . Since BMMC representthe in vitro equivalent of mucosai mast cells these data suggestthat IgE-activated mucosai mast cells can bias an emerging Tcell dependent Immune response towards a Th2 dominated reactionby the initial production of IL-4. |
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Keywords: | IL-4 IL-12 mucosal mast cells Th differentiation |
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