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International Immunology Advance Access originally published online on January 30, 2007
International Immunology 2007 19(3):305-310; doi:10.1093/intimm/dxl147
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

The initial response of CD4+ IL-4-producing cells

Junping Xin1, Keitaro Ohmori2,3, Jun Nishida2,3, Yuechun Zhu4,1 and Hua Huang2,3,*

1 Department of Cell Biology, Loyola University Chicago School of Medicine, Maywood, IL 60153, USA
2 Division of Allergy and Immunology, Department of Medicine
3 Department of Integrated Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, 1400 Jackson Street, Denver, CO 80206, USA
4 Present address: Department of Biochemistry and Molecular Biology, Kuming Medical College, Kuming, Yunnan 650031, People’s Republic of China

Correspondence to: H. Huang; E-mail: huangh{at}njc.org

Naive CD4+ T cells were reported to produce small amounts of IL-4 in vitro, which are implicated to be sufficient to initiate Th2 response in vivo. However, IL-4-producing naive CD4+ T cells are difficult to study in vivo because they are present in low numbers shortly after the first antigen exposure. Here, we used IL-4/green fluorescence protein (GFP) reporter mice (G4 mice) to track the initial response of CD4+ IL-4-producing cells. We first established a flow cytometry method to estimate the number of GFP+ cells. We demonstrated the effectiveness of this method by showing that the responding CD4+GFP+ cells exhibited an activated phenotype, possessed the capacity to express IL-5 and IL-13, but not IFN-{gamma} mRNA, and showed enhanced levels of GATA3 and c-maf mRNA expression. More importantly, we showed that the cell lines derived from FACS-sorted CD4+GFP+ cells were antigen specific. By using this newly established method, we showed that the majority of responding GFP+ cells were CD4+ T cells. Our study provides direct ex vivo evidence to show that a small percent of CD4+ T cells that have no previous experience of antigenic stimulation might produce IL-4 to initiate Th2 response.

Keywords: CD4+ T cells, IL-4/GFP reporter mice, initial IL-4 production

* This author is a former faculty member of Loyola University Chicago School of Medicine.

Transmitting editor: K. Murphy

Received 3 February 2006, accepted 21 December 2006.


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