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

Abstract

Activation of nalve dense CD4⁺ T cells by plate-bound anti-CD3 antibodies favors the development of T_h1 cells which, upon re-stimulation, produce significant amounts of INF-γ but no IL-4. However, co-activation of such naive T cells in the presence of IgE [anti-dlnitrophenyl (DNP)]-loaded bone marrow-derived mast cells (BMMC) on plates coated with anti-CD3 antibodies and DNP-BSA led to the development of IL-4-produclng T_h2 cells. The same result could be observed if irradiated (800 rad) BMMC were applied as co-stimulators. Moreover, BMMC could be replaced by the supernatant of IgE-activated BMMC suggesting that a soluble mediator, presumably IL-4, was responsible for this effect. This assumption was substantiated using neutralizing anti-IL-4 antibodies which abolished the BMMC-medlated T_h2 development in all cases. Addition of IL-12, a cytokine that was shown to antagonize the T_h2-promoting effect of IL-4 in vivo, could not inhibit the development of IL-4-producing T cells, but gave rise to a T cell population which produced relatively high amounts of IL-4 and IFN-γ. Since BMMC represent the in vitro equivalent of mucosai mast cells these data suggest that IgE-activated mucosai mast cells can bias an emerging T cell dependent Immune response towards a T_h2 dominated reaction by the initial production of IL-4.