Basophils initiate IL-4 production during a memory T-dependent response.
Experiments were performed to characterize and identify the cellular sources of the secondary interleukin (IL)-4 response to a T cell-dependent antigen. Mice were primed by immunization with goat anti-mouse immunoglobulin (Ig)D antibody (GaMD), which stimulates naive CD4+ T cells to secrete IL-4 in 3-4 d. When challenged with goat serum 14 d after immunization, GaMD-primed mice generated an IL-4 response that exceeded the primary response by approximately 100-fold, started in <2 h, and lasted for 4 d. Studies with 4get mice, in which cells with an accessible Il4 gene express a green fluorescent protein (GFP), revealed CD4+ memory T cells, natural killer T cells, basophils, mast cells, and eosinophils as possible rapid producers of IL-4. GFP(+)CD4+ T cells and basophils expanded more in the spleen than the other cell types during the primary response to GaMD. Quantitation of in vivo IL-4 production by the in vivo cytokine capture assay after individual cell types were selectively stimulated or deleted demonstrated that basophils and memory CD4+ T cells account for most of the secondary IL-4 response, with basophils initiating that response through IgE/FcepsilonRI-mediated signaling but secreting IL-4 for <4 h and memory T cells secreting IL-4 within 4 h and continuing to secrete this cytokine for 4 d.
Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Marat V
MV
Khodoun
Tatyana
T
Orekhova
Crystal
C
Potter
Suzanne
S
Morris
Fred D
FD
Finkelman
D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D053818:Chymases; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007114:Immunization; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012697:Serine Endopeptidases / Q000097:blood; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
D016207:Cytokines; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D012697:Serine Endopeptidases; D053818:Chymases