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Basophils contribute to TH2-IgE responses in vivo via IL-4 production and presentation of peptide–MHC class II complexes to CD4+ T cells

Abstract

Basophils express major histocompatibility complex class II, CD80 and CD86 and produce interleukin 4 (IL-4) in various conditions. Here we show that when incubated with IL-3 and antigen or complexes of antigen and immunoglobulin E (IgE), basophils internalized, processed and presented antigen as complexes of peptide and major histocompatibility complex class II and produced IL-4. Intravenous administration of ovalbumin-pulsed basophils into naive mice 'preferentially' induced the development of naive ovalbumin-specific CD4+ T cells into T helper type 2 (TH2) cells. Mice immunized in this way, when challenged by intravenous administration of ovalbumin, promptly produced ovalbumin-specific IgG1 and IgE. Finally, intravenous administration of IgE complexes rapidly induced TH2 cells only in the presence of endogenous basophils, which suggests that basophils are potent antigen-presenting cells that 'preferentially' augment TH2-IgE responses by capturing IgE complex.

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Figure 1: Splenic basophils induce TH2 cells in neutral culture conditions.
Figure 2: Bone marrow–derived basophils induce TH2 cells in neutral culture conditions.
Figure 3: IgE complex enhances uptake of OVA by basophils.
Figure 4: Intravenous administration of OVA-pulsed basophils induces a TH2 response.
Figure 5: Intravenous administration of antigen-IgE complex induces TH2 responses.

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Acknowledgements

We thank W.E. Paul and H. Yamane for suggestions after critical reading of this manuscript and Y. Taki, H. Seki and S. Futatsugi-Yumikura for technical assistance. Supported by The Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research on Priority Areas 18073016 and Hitech Research Center Grant), the Japan Society for the Promotion of Science (Grants-in-Aid for Scientific Research 20390145 and 19390121) and the Japanese Ministry of Health, Labor and Welfare (Grants for Research on Emerging and Re-emerging Infectious Diseases).

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Contributions

K.N. and T.Y. envisaged the possible APC function of basophils; T.Y. and K.N. designed the experiments; T.Y. did the main part of this study and analyzed the data; K.Y., M.N. and Y.I. helped with some experimental procedures; H.T. and Y.F. analyzed human cells; and T.Y. prepared the draft of manuscript and K.N. completed it.

Corresponding author

Correspondence to Kenji Nakanishi.

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Yoshimoto, T., Yasuda, K., Tanaka, H. et al. Basophils contribute to TH2-IgE responses in vivo via IL-4 production and presentation of peptide–MHC class II complexes to CD4+ T cells. Nat Immunol 10, 706–712 (2009). https://doi.org/10.1038/ni.1737

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