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Genetic analysis of basophil function in vivo
Brandon M Sullivan1,2,8, Hong-Erh Liang1,2,8, Jennifer K Bando1,2, Davina Wu1,2, Laurence E Cheng3, James K McKerrow4,5, Christopher D C Allen6,7 & Richard M Locksley1,2,6,7
Contributions by basophils to allergic and helminth immunity remain incompletely defined. Using sensitive interleukin 4 (Il4) reporter alleles, we demonstrate here that basophil IL-4 production occurs by a CD4+ T celldependent process restricted to the peripheral tissues affected. We genetically marked and achieved specific deletion of basophils and found that basophils did not mediate T helper type 2 (TH2) priming in vivo. Two-photon imaging confirmed that basophils did not interact with antigen-specific
T cells in lymph nodes but engaged in prolonged serial interactions with T cells in lung tissues. Although targeted deletion of IL-4 and IL-13 in either CD4+ T cells or basophils had a minimal effect on worm clearance, deletion from both lineages demonstrated a nonredundant role for basophil cytokines in primary helminth immunity.
2011Nature America, Inc. All rights reserved.
Helminth infections, which affect nearly 2.9 billion humans worldwide1, elicit a stereotypical immune response with features shared by allergic and asthmatic reactions, including higher serum concentrations of immunoglobulin E (IgE), excessive mucus production and tissue inflammation dominated by polarized T helper type 2 (TH2)
cells, eosinophils, mast cells and basophils. The linked cytokines inter-leukin 4 (IL-4) and IL-13, as well as their shared signaling components, the IL-4 receptor -chain and the transcription factor STAT6, are required for allergic and anti-helminth immunity2,3. Although CD4+ T cells are required and TH2 cells can produce these cytokines, innate sources of IL-4 and IL-13, such as basophils4 or lineage-negative IL-25- and IL-33-responsive cells57 (called innate type 2 helper cells here) can contribute to primary anti-helminth immunity. Immunohistochemical techniques are not adequate at present to discern cytokine-producing cells in situ and thus a thorough assessment of their spatial and temporal relationships in tissues during the host response has been lacking.
Basophils are proposed to mediate B cell isotype switching and to drive the differentiation of CD4+ helper T cells810. Several studies have indicated that basophils are antigen-presenting cells (APCs) that are necessary and sufficient for TH2 priming1113, although this has been challenged by others1417. Despite such progress, the demonstration of basophil...