The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8+ T Cells in Response to a Lethal Poxvirus Infection

• Published in: Immunity (Cambridge, Mass.) Mass.), 2015-12, Vol.43 (6), p.1112-1124
• Main Authors: Rapaport, Aaron S., Schriewer, Jill, Gilfillan, Susan, Hembrador, Ed, Crump, Ryan, Plougastel, Beatrice F., Wang, Yaming, Le Friec, Gaelle, Gao, Jian, Cella, Marina, Pircher, Hanspeter, Yokoyama, Wayne M., Buller, R. Mark L., Colonna, Marco
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; CD8+ T cell; CD8-Positive T-Lymphocytes - immunology; cytokine; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Disease Models, Animal; Ectromelia virus; Flow Cytometry; Infections; inhibitory receptor; Killer Cells, Natural - immunology; Kinases; Ligands; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; NK cell; NK Cell Lectin-Like Receptor Subfamily C - immunology; NKG2A; Oligonucleotide Array Sequence Analysis; Peptides; Poxviridae Infections - immunology; Poxvirus; Real-Time Polymerase Chain Reaction; Viral infections; virus
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2015.11.005

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. [Display omitted] •Control of lethal poxvirus infection requires NKG2A•NKG2A limits excessive activation and apoptosis within virus-specific CD8+ T cells•NKG2C and NKG2E are not expressed on the surface of mouse NK cells and CD8+ T cells•Qa-1 is preferentially expressed on B cells in ECTV-infected tissues NK cells and T cells express a variety of inhibitory receptors that differentially regulate cell survival and effector functions. Here, Colonna and colleagues demonstrate that NKG2A limits excessive activation and apoptosis of CD8+ T cells in vivo and that this function is required to resist infection with ectromelia virus.