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Nat Immunol. 2001 Nov;2(11):1054-60.

IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice.

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  • 1Department of Dermatology and Allergology, Ludwig-Maximilians-University Munich, Frauenlobstr. 9-11, 80337 Munich, Germany.


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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