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 immunopatbologv, 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 pathologv upon CD8(+) T cell-mediated clearance in influenza pneumonia. Furthermore, blockade of NKG2A ligation resulted in the enhancement of lung injuiy induced by CD8(+) effect or 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.