Article: article from journal or magazin.
Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells.
Proceedings of the National Academy of Sciences of the United States of America
CD8+ memory T cells have recently been recognized as playing a key role in natural immunity against unrelated viral infections, a phenomenon referred to as "heterologous antiviral immunity." We now provide data that the cellular immunological interactions that underlie such heterologous immunity can play an equally important role in regulating T helper 2 immune responses and protecting mucosal surfaces from allergen-induced inflammation. Our data show that CD8+ T cells, either retained in the lung after infection with influenza virus, or adoptively transferred via the intranasal route can suppress allergic airway inflammation. The suppression is mediated by IFN-gamma, which acts to reduce the activation level, T helper 2 cytokine production, airways hyperresponsiveness, and migration of allergen-specific CD4+ T cells into the lung, whereas the systemic and draining lymph node responses remain unchanged. Of note, adoptive transfer of previously activated transgenic CD8+ T cells conferred protection against allergic airway inflammation, even in the absence of specific-antigen. Airway resident CD8+ T cells produced IFN-gamma when directly exposed to conditioned media from activated dendritic cells or the proinflammatory cytokines IL-12 and IL-18. Taken together these data indicate that effector/memory CD8+ T cells present in the airways produce IFN-gamma after inflammatory stimuli, independent of specific-antigen, and as a consequence play a key role in modifying the degree and frequency of allergic responses in the lung.
Adoptive Transfer, Animals, Bronchitis/immunology, Bronchoalveolar Lavage Fluid, Bystander Effect, CD4-Positive T-Lymphocytes/cytology, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, Culture Media, Conditioned, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Hypersensitivity/immunology, Immunologic Memory, Interferon-gamma/physiology, Lung/cytology, Lung/immunology, Lymphocyte Activation, Mice, Mice, Inbred C57BL
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