The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8+ T Cells in Response to a Lethal Poxvirus Infection
| Autor: | Wayne M. Yokoyama, Marco Colonna, Ryan W. Crump, Jill Schriewer, Ed Hembrador, Aaron S. Rapaport, Hanspeter Pircher, Jian Gao, Gaelle Le Friec, Béatrice Plougastel, R. Mark L. Buller, Yaming Wang, Susan Gilfillan, Marina Cella |
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| Rok vydání: | 2015 |
| Předmět: |
Cytotoxicity
Immunologic medicine.medical_treatment T cell viruses Immunology virus Poxviridae Infections CD8-Positive T-Lymphocytes NKG2A Real-Time Polymerase Chain Reaction Virus Article 03 medical and health sciences Mice 0302 clinical medicine cytokine medicine Cytotoxic T cell Animals Immunology and Allergy NK cell Receptor 030304 developmental biology Oligonucleotide Array Sequence Analysis Mice Knockout 0303 health sciences biology Ectromelia virus CD8+ T cell inhibitory receptor biology.organism_classification Flow Cytometry Virology 3. Good health Killer Cells Natural Mice Inbred C57BL Disease Models Animal Cytokine medicine.anatomical_structure Infectious Diseases NK Cell Lectin-Like Receptor Subfamily C CD8 030215 immunology |
| Zdroj: | Immunity. 43(6):1112-1124 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2015.11.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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