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Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response

Nature Immunology volume 10, pages 713–720 (2009)Cite this article

Abstract

T helper type 2 (TH2)-mediated immune responses are induced after infection with multicellular parasites and can be triggered by a variety of allergens. The mechanisms of induction and the antigen-presenting cells involved in the activation of TH2 responses remain poorly defined, and the innate immune sensing pathways activated by parasites and allergens are largely unknown. Basophils are required for the in vivo induction of TH2 responses by protease allergens. Here we show that basophils also function as antigen-presenting cells. We show that although dendritic cells were dispensable for allergen-induced activation of TH2 responses in vitro and in vivo, antigen presentation by basophils was necessary and sufficient for this. Thus, basophils function as antigen-presenting cells for TH2 differentiation in response to protease allergens.

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Figure 1: Basophils are necessary for TH2 differentiation in vitro, but DCs are not.
Figure 2: Basophil-mediated TH2 differentiation in vitro is dependent on IL-4.
Figure 3: Basophils express and upregulate MHC class II after papain stimulation and can form synapses with T cells in vitro.
Figure 4: Basophils are able to endocytose soluble antigens but not particulate antigens.
Figure 5: Migratory DCs are not necessary for basophil migration or TH2 differentiation after papain immunization.
Figure 6: DCs and DC-derived MHC class II are not required for TH2 differentiation after papain immunization.
Figure 7: Antigen presentation by basophils is sufficient for TH2 differentiation.

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Acknowledgements

We thank I. Weissman (Stanford University) for H-2k–Bcl-2 mice; K. Bottomly (Yale University) for DO11.10 × 4get transgenic mice; A. Iwasaki (Yale University) for mice and reagents; S. Holley, C. Annicelli and M. Kotas for technical assistance; and J. Kagan and D. Hargreaves for experimental input. Supported by the US National Institutes of Health (Medical Scientist Training Program TG2T32GM07205 to C.L.S. and R01 AI46688 and R01 AI055502 to R.M.), the Howard Hughes Medical Institute (R.M.) and the Sandler Program in Asthma Research.

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    Caroline L Sokol, Ngoc-Quynh Chu, Shuang Yu, Simone A Nish & Ruslan Medzhitov

  2. Immunology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Terri M Laufer

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  1. Caroline L Sokol
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Contributions

C.L.S. and R.M. designed the experiments; C.L.S., N.-Q.C., S.Y. and S.A.N. did the experiments; C.L.S. and R.M. analyzed the data and wrote the manuscript; and T.M.L. provided CD11c-IABB mice.

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Correspondence to Ruslan Medzhitov.

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Sokol, C., Chu, NQ., Yu, S. et al. Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol 10, 713–720 (2009). https://doi.org/10.1038/ni.1738

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