IL-12-dependent inducible expression of the CD94/NKG2A inhibitory receptor regulates CD94/NKG2C+ NK cell function.
The inhibitory CD94/NKG2A and activating CD94/NKG2C killer lectin-like receptors specific for HLA-E have been reported to be selectively expressed by discrete NK and T cell subsets. In the present study, minor proportions of NK and T cells coexpressing both CD94/NKG2A and CD94/NKG2C were found in fresh peripheral blood from adult blood donors. Moreover, CD94/NKG2A surface expression was transiently detected upon in vitro stimulation of CD94/NKG2C+ NK cells in the presence of irradiated allogeneic PBMC or rIL-12. A similar effect was observed upon coculture of NKG2C+ NK clones with human CMV-infected autologous dendritic cell cultures, and it was prevented by an anti-IL-12 mAb. NKG2A inhibited the cytolytic activity of NKG2C+ NK clones upon engagement either by a specific mAb or upon interaction with a transfectant of the HLA class I-deficient 721.221 cell line expressing HLA-E. These data indicate that beyond its constitutive expression by an NK cell subset, NKG2A may be also transiently displayed by CD94/NKG2C+ NK cells under the influence of IL-12, providing a potential negative regulatory feedback mechanism.
Sáez-Borderías
Andrea
A
Molecular Immunopathology Unit, Universitat Pompeu Fabra, and Institut Municipal d'Investigació Mèdica-Hospital del Mar, Barcelona, Spain.
Romo
Neus
N
Magri
Giuliana
G
Gumá
Mónica
M
Angulo
Ana
A
López-Botet
Miguel
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000276:immunology*; D025461:Feedback, Physiological / Q000276:immunology; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D015533:Transcriptional Activation / Q000276:immunology*; D055815:Young Adult
C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D018664:Interleukin-12