The Journal of Experimental Medicine
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Published 4 October 2004. doi:10.1084/jem.20040598
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 7, 857-870
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Basophils Initiate IL-4 Production during a Memory T-dependent Response

Marat V. Khodoun, Tatyana Orekhova1, Crystal Potter1, Suzanne Morris1,2, and Fred D. Finkelman1,2,3

1 Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267
2 Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220
3 Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229

Address correspondence to Fred Finkelman, Dept. of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267. Phone: (513) 558-4701; Fax: (513) 558-3799; email: ffinkelman{at}pol.net

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 ~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/Fc{varepsilon}RI-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.

Key Words: cytokine • allergy • NKT cell • eosinophil • mast cell

Abbreviations used in this paper: GaMD, goat anti–mouse IgD antibody; IVCCA, in vivo cytokine capture assay; MMCP1, mouse mast cell protease 1.


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