IL-4 mRNA 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 (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.
Frandji
P
P
Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.
Mourad
W
W
Tkaczyk
C
C
Singer
M
M
David
B
B
Colle
J H
JH
Mécheri
S
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001854:Bone Marrow Cells / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D010455:Peptides / Q000276:immunology; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D015847:Interleukin-4