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MHC class II–dependent basophil–CD4+ T cell interactions promote TH2 cytokine–dependent immunity

Nature Immunology volume 10, pages 697–705 (2009)Cite this article

Abstract

Dendritic cells can prime naive CD4+ T cells; however, here we demonstrate that dendritic cell–mediated priming was insufficient for the development of T helper type 2 cell–dependent immunity. We identify basophils as a dominant cell population that coexpressed major histocompatibility complex class II and interleukin 4 message after helminth infection. Basophilia was promoted by thymic stromal lymphopoietin, and depletion of basophils impaired immunity to helminth infection. Basophils promoted antigen-specific CD4+ T cell proliferation and interleukin 4 production in vitro, and transfer of basophils augmented the population expansion of helminth-responsive CD4+ T cells in vivo. Collectively, our studies suggest that major histocompatibility complex class II–dependent interactions between basophils and CD4+ T cells promote T helper type 2 cytokine responses and immunity to helminth infection.

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Figure 1: Restriction of MHC class II expression to CD11c+ DC is insufficient to promote type 2 immunity to intestinal helminth infection.
Figure 2: Blockade of IFN-γ in MHC IICD11c mice restores TH2 cytokine–dependent immunity to T. muris infection.
Figure 3: FcεRI+CD49b+ basophils coexpress MHC class II and IL-4–eGFP.
Figure 4: Depletion of FcεRI+ cells in vivo results in impaired immunity to T. muris infection.
Figure 5: TSLP treatment selectively increases basophil frequencies in vivo.
Figure 6: Basophils promote MHC class II–dependent antigen-specific CD4+ T cell proliferation and TH2 cytokine production in vitro.
Figure 7: IL-4–eGFP+ MHC class II–positive basophils are recruited to the draining lymph node after exposure to S. mansoni eggs, and they augment CD4+ T cell proliferation in vivo.

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Acknowledgements

We thank M. Mohrs (Trudeau Institute) for 4get mice; A. Troy for critical reading of this manuscript; E. Tait for generating the bone marrow chimeras; and the University of Pennsylvania Flow Cytometry Core and Center for Molecular Studies in Digestive and Liver Diseases Morphology Core for assistance with sorting and immunofluorescence staining. Supported by the National Institutes of Health (Artis lab: AI61570 and AI074878 to D.A., T32 training grant AI007532-08 to J.G.P., F31 training grant GM082187 to S.A.S. and T32 CA09140-30 to B.C.T.; Pearce lab: AI32573 and AI53825; and Laufer lab), the Burroughs Wellcome Fund (Artis lab: D.A.), the National Institute of Diabetes and Digestive Kidney Diseases (Artis lab: DK50306), the Crohn's and Colitis Foundation of America (Artis lab: D.A. and M.G.N.) and the University of Pennsylvania (Artis lab: D.A. and T.M.L.).

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Authors and Affiliations

  1. Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Jacqueline G Perrigoue, Steven A Saenz, Mark C Siracusa, Betsy C Taylor, Paul R Giacomin, Meera G Nair, Yurong Du, Edward J Pearce & David Artis

  2. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Eric J Allenspach & Terri M Laufer

  3. Department of Pathology and Laboratory Medicine, The Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, Canada

    Colby Zaph

  4. Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands

    Nico van Rooijen

  5. Inflammation Research, Amgen, Seattle, Washington, USA

    Michael R Comeau

  6. Philadelphia Veterans Affairs Medical Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Terri M Laufer

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Perrigoue, J., Saenz, S., Siracusa, M. et al. MHC class II–dependent basophil–CD4+ T cell interactions promote TH2 cytokine–dependent immunity. Nat Immunol 10, 697–705 (2009). https://doi.org/10.1038/ni.1740

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