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Disrupting Il13 impairs production of IL-4 specified by the linked allele

Nature Immunology volume 2, pages 461–466 (2001)Cite this article

Abstract

Interleukin 13–deficient (IL-13−/−) mice express a defect in priming for IL-4 production that is not corrected by adding IL-13 to the priming culture. This is partly accounted for by the consumption of IL-4 without endogenous replacement during culture of IL-13−/− CD4+ T cells. We examined cells from mice in which disrupted Il13 was linked to wild-type Il4 on one chromosome and wild-type Il13 was linked to a “knocked-in” green fluorescent protein (Gfp) gene in the Il4 locus. Our results show that the deficit in IL-4 production was due, at least in part, to a cis effect, in which disrupted Il13 diminished IL-4 production from the linked Il4 gene.

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Figure 1: TH2-primed IL-13−/− cells make less IL-4 than wild-type cells.
Figure 2: IL-4Rα chain and γc chain are expressed normally on IL-13−/− cells.
Figure 3: “Fresh” IL-13−/− cells signal normally in response to IL-4.
Figure 4: IL-4Rα phosphorylation is diminished in IL-13−/− cells at 48 h, but is restored by addition of IL-4.
Figure 5: Additional IL-4 enhances priming of IL-13−/− cells.
Figure 6: Primed T cells from (IL-13−/− × GFP)F1 mice develop fewer IL-4–producing cells than T cells from (BALB/c × GFP)F1 or (129 × GFP)F1 mice do.

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Acknowledgements

We thank Shirley Starnes for editorial assistance.

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Author notes

  1. Christophe Pannetier

    Present address: Institut Pasteur, Paris, France

Authors and Affiliations

  1. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA

    Liying Guo, Jane Hu-Li, Jinfang Zhu, Christophe Pannetier, Cynthia Watson & William E. Paul

  2. Lorantis, Babraham, Cambridge, UK

    Grahame J. McKenzie

  3. Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    Andrew N. J. McKenzie

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Corresponding author

Correspondence to William E. Paul.

Supplementary information

Web Figure 1.

IL-13-/-cells produce less IL-4 than wild-type cells. Lymph node CD4 T cells (105/ml) were cultured with irradiated APCs (106/ml) in anti-CD3, anti-CD28 and IL-2 in the presence of IL-4 (500 pg/ml), anti–IL-12 an IFN-γ. IL-4 concentration in supernatant fluid at days 2 and 4 was bioassayed. (GIF 11 kb)

Web Figure 2.

Disruption of Il13 has little effect on RAD50. Lymph node CD4 T cells from IL-13-/- or BALB/c mice were purified and primed under TH1 and TH2 conditions. RAD50 mRNA levels were examined by RT-PCR using twofold dilutions of "input" RNA. (JPG 18 kb)

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Guo, L., Hu-Li, J., Zhu, J. et al. Disrupting Il13 impairs production of IL-4 specified by the linked allele. Nat Immunol 2, 461–466 (2001). https://doi.org/10.1038/87778

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