Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells
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.
Keywords: Adoptive Transfer ; Animals ; Bronchitis/*immunology ; Bronchoalveolar Lavage Fluid ; *Bystander Effect ; CD4-Positive T-Lymphocytes/cytology/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Culture Media, Conditioned ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Hypersensitivity/*immunology ; *Immunologic Memory ; Interferon-gamma/physiology ; Lung/cytology/*immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL
Marsland, Benjamin J Harris, Nicola L Camberis, Mali Kopf, Manfred Hook, Sarah M Le Gros, Graham Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6116-21. Epub 2004 Apr 12.
Record created on 2010-01-06, modified on 2016-08-08