COACTIVATION OF NAIVE CD4(+) T-CELLS AND BONE-MARROW-DERIVED MAST-CELLS RESULTS IN THE DEVELOPMENT OF T(H)2 CELLS

Activation of naive dense CD4(+) T cells by plate-bound anti-CDS antibodies favors the development of T(h)1 cells which, upon re-stimulation, produce significant amounts of IFN-gamma but no IL-4. However, co-activation of such naive T cells in the presence of IgE [anti-dinitrophenyl (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-producing T(h)2 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-mediated T(h)2 development in all cases. Addition of IL-12, a cytokine that was shown to antagonize the T(h)2-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-gamma. Since BMMC represent the in vitro equivalent of mucosal mast cells these data suggest that IgE-activated mucosal mast cells can bias an emerging T cell dependent immune response towards a T(h)2 dominated reaction by the initial production of IL-4.