Cutting edge: engagement of NKG2A on CD8+ effector T cells limits immunopathology in influenza pneumonia.

Influenza pneumonia results in considerable lung injury, a significant component of which is mediated by CD8+ T cell Ag recognition in the distal airways and alveoli. TNF-alpha produced by Ag-specific CD8+ T cells appears primarily responsible for this immunopathology, and we have examined the negative regulation of CD8+ TNF production by CD94/NKG2A engagement with its receptor, Qa-1b. TNF production by antiviral CD8+ T cells was significantly enhanced by NKG2A blockade in vitro, and mice deficient in the NKG2A ligand, Qa-1b, manifested significantly greater pulmonary pathology upon CD8+ T cell-mediated clearance in influenza pneumonia. Furthermore, blockade of NKG2A ligation resulted in the enhancement of lung injury induced by CD8+ effector cell recognition of alveolar Ag in vivo in the absence of infectious virus. These data demonstrate that CD94/NKG2A transduces a biologically important signal in vivo to activated CD8+ T cells that limits immunopathology in severe influenza infection.