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Mice lacking the IFN-gamma receptor have impaired ability to resolve a lung eosinophilic inflammatory response associated with a prolonged capacity of T cells to exhibit a Th2 cytokine profile.
Journal of Immunology
Date de publication
To investigate the modulatory role of IFN-gamma on the induction and maintenance of Th2 mucosal immunity in vivo, experiments were performed in mice lacking the IFN-gamma R. Aerosol OVA challenge of immunized wild-type mice resulted in an infiltration of eosinophils into the lung, associated with the ex vivo production of Th2 cytokines (IL-4 and IL-5) from purified lung Thy1.2+ cells stimulated via the CD3/TCR complex. However, while immunized IFN-gamma R-deficient mice exhibited elevated levels of IgE, IgG1, and reduced levels of IgG2a compared with wild-type mice, there was no difference in the recruitment of eosinophils into the lung or the production of IL-4 and IL-5 from lung T cells on day 3. In contrast, up to 2 mo after a single Ag challenge, eosinophils were still present in the lungs of IFN-gamma R-deficient, but not wild-type, mice. Likewise, lung-derived T cells from IFN-gamma R-deficient mice produced higher levels of IL-4 and IL-5, both at 1 and 2 mo after OVA challenge compared with T cells from wild-type mice. We conclude that endogenous IFN-gamma regulates the humoral isotype Ab pattern, but does not modulate the commitment of T cells to a Th2 phenotype in vivo or the acute infiltration of eosinophils to the lung. However, in the absence of IFN-gamma-mediated signaling, there is a transition from a spontaneously resolving to a persisting eosinophilic inflammation of the lungs, associated with a sustained capacity of lung T cells to secrete a Th2 cytokine profile.
Animals, Antigens, CD/genetics, Antigens, CD/metabolism, Cytokines/biosynthesis, Eosinophils/immunology, Eosinophils/pathology, Female, Immunoglobulin E/biosynthesis, Immunoglobulin E/blood, Immunoglobulin G/biosynthesis, Immunoglobulin G/blood, Immunologic Deficiency Syndromes/blood, Immunologic Deficiency Syndromes/genetics, Interferon-gamma/deficiency, Lung/pathology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Interferon/deficiency, Receptors, Interferon/genetics, Th2 Cells/metabolism
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