IL-4 MESSENGER-RNA TRANSCRIPTION IS INDUCED IN MOUSE BONE-MARROW-DERIVED MAST-CELLS THROUGH AN MHC CLASS II-DEPENDENT SIGNALING PATHWAY

We have previously shown that mouse bone marrow-derived mast cells (BM MC) can process and present immunogenic peptides to CD4 T cells. Here, we report on a T cell-dependent MHC class II-mediated mast cell activ ation resulting in IL-4 transcription and protein release. Presentatio n of optimal doses of ovalbumin peptide 323-339 resulted in IL-2 produ ction by a specific T cell hybridoma and increase in IL-4 mRNA transcr iption in mast cells. IL-4 mRNA transcription increased by 200-fold in mast cells treated in IL-3/IL-4/ granulocyte-macrophage colony-stimul ating factor (high presenters) whereas only a tenfold increase or no i ncrease were obtained with IL-3/IL-4/IFN-gamma- or IL-3-treated mast c ells (low presenters), respectively. Induction of IL-4 mRNA transcript ion in purified mast cells by direct ligation of MHC class II molecule s, using anti-I-A and anti-I-E-coated beads, indicates that MHC class II molecules are critical in this signaling pathway. However, when com pared to T cells, anti-MHC class II-coated beads were less efficient, indicating a potential role of accessory molecules in this mast cell a ctivation process. IgE-independent IL-4 production by mast cells as a result of cognate interaction with CD4 T cells could be critical for t he development of type 2 responses. This novel mechanism may contribut e to the induction and/or amplification of specific IgE-mediated aller gic responses.