Co-activation of naive CD4+ T cells and bone marrow-derived mast cells results in the development of Th2 cells

Activation of nalve dense CD4⁺ T cells by plate-bound anti-CD3antibodies favors the development of T_h1 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 T_h2 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 T_h2 development in all cases. Addition of IL-12,a cytokine that was shown to antagonize the T_h2-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 T_h2 dominated reactionby the initial production of IL-4.