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.
Zhou
Jing
J
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Matsuoka
Mitsuo
M
Cantor
Harvey
H
Homer
Robert
R
Enelow
Richard I
RI
D000818:Animals; D000941:Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D009980:Influenza A virus; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D011024:Pneumonia, Viral / Q000276:immunology* / Q000473:pathology; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell
D000941:Antigens; D015395:Histocompatibility Antigens Class I; C527057:Klrc1 protein, mouse; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; C032907:Q surface antigens; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell