Abstract
Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type 1 (TH1) responses, or IL-4, which induces TH2 cells and susceptibility. Paradoxically, we show here that when present during the initial activation of dendritic cells (DCs) by infectious agents, IL-4 instructed DCs to produce IL-12 and promote TH1 development. This TH1 response established resistance to Leishmania major in susceptible BALB/c mice. When present later, during the period of T cell priming, IL-4 induced TH2 differentiation and progressive leishmaniasis in resistant mice. Because immune responses developed via the consecutive activation of DCs and then T cells, the contrasting effects of IL-4 on DC development and T cell differentiation led to immune responses that had opposing functional phenotypes.
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Acknowledgements
We thank W. E. Paul, E. M. Shevach (Laboratory of Immunology, NIAID, NIH), G. Riethmüller and T. Brocker (Department of Immunology, Munich) for helpful discussions and critically reading the manuscript and B. von Restorff for technical assistance. Supported by the Deutsche Forschungsgemeinschaft RO 764/8-1 and 676/1, SFB 217 and SFB 456, the Wilhelm Sander-Stiftung (97.041.2) and the Swiss National Science Fdt.
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Biedermann, T., Zimmermann, S., Himmelrich, H. et al. IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice. Nat Immunol 2, 1054–1060 (2001). https://doi.org/10.1038/ni725
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DOI: https://doi.org/10.1038/ni725
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