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.
Nat Commun. 2018 Feb 26;9(1):824. doi: 10.1038/s41467-018-03243-7.
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 CD38HLA-DRPD-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 CD38HLA-DRCD8 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 CD38HLA-DRCD8 T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38HLA-DRCD8 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.
严重的甲型流感病毒（IAV）感染与免疫功能障碍有关。在这里，我们展示了来自因感染禽流感 H7N9、季节性 IAV 和流感疫苗而住院的患者的循环 CD8 T 细胞谱。患者的存活反映了高度激活的 CD38HLA-DRPD-1 CD8 T 细胞的早期、短暂流行，而在最终致命的病例中则发现了这种细胞的长期持续存在。对激活的 CD38HLA-DRCD8 T 细胞进行单细胞 T 细胞受体（TCR）-αβ 分析表明，存活和致命 H7N9 患者的 TCRαβ 多样性相似，但克隆扩展动力学不同。在因疾病而死亡的患者的 CD38HLA-DRCD8 T 细胞中，在转录组水平（通过单细胞 RNAseq 检测到）发现了与迟发性克隆扩展相关的早期二分法，这表明在致命疾病开始时，CD38HLA-DRCD8 T 细胞的分化途径就存在分歧。我们的研究表明，需要具有适当转录组特征的交叉反应性流感特异性 TCRαβ 克隆型的有效扩展，以早期预防严重流感疾病。
