IL-4 mRNA transcription is induced in mouse bone marrow-derived mast cells through an MHC class II-dependent signaling pathway

Abstract

We have previously shown that mouse bone marrow-derived mast cells (BMMC) can process and present immunogenic peptides to CD4 T cells. Here, we report on a T cell-dependent MHC class II-mediated mast cell activation resulting in IL-4 transcription and protein release. Presentation of optimal doses of ovalbumin peptide 323-339 resulted in IL-2 production by a specific T cell hybridoma and increase in IL-4 mRNA transcription in mast cells. IL-4 mRNA transcription increased by 200-fold in mast cells treated in IL-3/IL-4/granulocyte-macrophage colony-stimulating factor (high presenters) whereas only a tenfold increase or no increase were obtained with IL-3/IL-4/IFN-gamma- or IL-3-treated mast cells (low presenters), respectively. Induction of IL-4 mRNA transcription in purified mast cells by direct ligation of MHC class II molecules, using anti-I-A and anti-I-E-coated beads, indicates that MHC class II molecules are critical in this signaling pathway. However, when compared to T cells, anti-MHC class II-coated beads were less efficient, indicating a potential role of accessory molecules in this mast cell activation process. IgE-independent IL-4 production by mast cells as a result of cognate interaction with CD4 T cells could be critical for the development of type 2 responses. This novel mechanism may contribute to the induction and/or amplification of specific IgE-mediated allergic responses.

MHC class II-dependent activation of CD4+ T cell hybridomas by human mast cells through superantigen presentation

“…Frandji et al have shown that BMMC, studied as APC, activated only a restricted spectrum of T cells compared with B cells [11]. However, the conditions for presentation of nominal antigen are fulfilled by BMMC which, in turn, were shown to undergo activation and to secrete IL-4 [11,12,32,47]. This raises the question of the influence of MC used as APC on the Th1/Th2 balance.…”

Mast Cells Enhance T Cell Activation: Importance of Mast Cell Costimulatory Molecules and Secreted TNF

“…For example, purified populations of mast cells can present Ags to T cells by either MHC class I-or class II-restricted mechanisms in vitro (8 -11), and contact with activated T cells in vitro can induce some mast cell populations to secrete histamine, TNF, and metalloproteinase 9 and to exhibit enhanced levels of IL-4 mRNA (12)(13)(14)(15). Besides representing a major potential source of TNF (16,17), which can have several effects that influence T cell recruitment, activation, and function (18 -21), at least some mast cells can produce many other factors, including CCL2, CCL3, CCL4, CCL5, XCL1, IL-16, and leukotriene B 4 , which also have the potential to enhance T cell recruitment to local inflammatory sites (5,(22)(23)(24)(25).…”

The mast cell and allergic diseases: role in pathogenesis and implications for therapy

“…Recently, thymic stromal lymphopoietin (TSLP), released by epithelial cells in response to physical injury and/or inflammatory cytokines, has been reported as a possible initiator of asthmatic responses through the potent stimulation of mast cells, to produce high levels of Th2 cytokines [51]. Mast cells are also known to present antigen, further providing a mechanism supporting Th2 differentiation and T cell activation [52][53][54][55]. In addition to the role of Th2-differentiated T cells, CD4…”