title: The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8⁺ T Cells in Response to a Lethal Poxvirus Infection.
abstract: CD8(+) T cells and NK cells protect from viral infections by killing virally infected cells and secreting interferon-γ. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses. NKG2A, which is encoded by Klrc1, is a lectin-like inhibitory receptor that is expressed as a heterodimer with CD94 on NK cells and activated CD8(+) T cells. Previous studies on the impact of CD94/NKG2A heterodimers on anti-viral responses have yielded contrasting results and the in vivo function of NKG2A remains unclear. Here, we generated Klrc1(-/-) mice and found that NKG2A is selectively required for resistance to ectromelia virus (ECTV). NKG2A functions intrinsically within ECTV-specific CD8(+) T cells to limit excessive activation, prevent apoptosis, and preserve the specific CD8(+) T cell response. Thus, although inhibitory receptors often cause T cell exhaustion and viral spreading during chronic viral infections, NKG2A optimizes CD8(+) T cell responses during an acute poxvirus infection.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Rapaport
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, 1402 South Grand Blvd, St. Louis, MO 63104, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Schriewer
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Gilfillan
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, 1402 South Grand Blvd, St. Louis, MO 63104, USA.
authors.forename: Ed
authors.initials: E
authors.lastname: Hembrador
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, 1402 South Grand Blvd, St. Louis, MO 63104, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Crump
authors.affiliation: Rheumatology Division, Department of Medicine, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Beatrice F
authors.initials: BF
authors.lastname: Plougastel
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Le Friec
authors.affiliation: Rheumatology Division, Department of Medicine, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.affiliation: Institute of Immunology, Center for Microbiology and Hygiene, University Medical Center Freiburg, Hermann-Herder Strasse 11, 79104 Freiburg, Germany.
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Pircher
authors.affiliation: Rheumatology Division, Department of Medicine, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA; Howard Hughes Medical Institute, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University Health Sciences Center, 1402 South Grand Blvd, St. Louis, MO 63104, USA.
authors.forename: R Mark L
authors.initials: RM
authors.lastname: Buller
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA. Electronic address: mcolonna@pathology.wustl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D011213:Poxviridae Infections / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D055654:NK Cell Lectin-Like Receptor Subfamily C
keywords: CD8(+) T cell; NK cell; NKG2A; cytokine; inhibitory receptor; virus