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.
Marsland
Benjamin J
BJ
Malaghan Institute of Medical Research, Wellington School of Medicine, 6002 Wellington, New Zealand. marsland@env.ethz.ch
Harris
Nicola L
NL
Camberis
Mali
M
Kopf
Manfred
M
Hook
Sarah M
SM
Le Gros
Graham
G
D019264:Adoptive Transfer; D000818:Animals; D001991:Bronchitis / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D024201:Bystander Effect; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL
D017077:Culture Media, Conditioned; D007371:Interferon-gamma