Clonally diverse CD38 + HLA-DR + CD8 + T cells persist during fatal H7N9 disease.

Autor: Wang Z; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China.; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Zhu L; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China., Nguyen THO; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Wan Y; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China., Sant S; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Quiñones-Parra SM; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Crawford JC; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA., Eltahla AA; School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, NSW, 2052, Australia., Rizzetto S; School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, NSW, 2052, Australia., Bull RA; School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, NSW, 2052, Australia., Qiu C; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China., Koutsakos M; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Clemens EB; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Loh L; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Chen T; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China., Liu L; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China., Cao P; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC, 3010, Australia., Ren Y; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China., Kedzierski L; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia., Kotsimbos T; Department of Respiratory Medicine, Alfred Hospital Health and Department Medicine, Monash University, 99 Commercial Road, Melbourne, VIC, 3004, Australia., McCaw JM; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC, 3010, Australia., La Gruta NL; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia.; Department of Biochemistry and Molecular Biology, Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia., Turner SJ; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia.; Department of Microbiology, Biomedical Discovery Institute, Monash University, Clayton, VIC, 3800, Australia., Cheng AC; Infection Prevention and Healthcare Epidemiology Unit, Alfred Health and School of Public Health and Preventive Medicine, 99 Commercial Road, Melbourne, VIC, 3004, Australia., Luciani F; School of Medical Sciences and The Kirby Institute, UNSW Sydney, Sydney, NSW, 2052, Australia., Zhang X; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China., Doherty PC; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia.; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA., Thomas PG; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA., Xu J; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China. xujianqing@shphc.org.cn., Kedzierska K; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, 201508, Shangai, China. kkedz@unimelb.edu.au.; Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Melbourne, VIC, 3010, Australia. kkedz@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Feb 26; Vol. 9 (1), pp. 824. Date of Electronic Publication: 2018 Feb 26.
DOI: 10.1038/s41467-018-03243-7
Abstrakt: Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8 + T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38 + HLA-DR + PD-1 + CD8 + T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38 + HLA-DR + CD8 + T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by single-cell RNAseq) is found in CD38 + HLA-DR + CD8 + T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38 + HLA-DR + CD8 + T cells from the outset during fatal disease. Our study proposes that effective expansion of cross-reactive influenza-specific TCRαβ clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.
Databáze: MEDLINE