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

ABSTRACT: 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)-?? analyses of activated CD38+HLA-DR+CD8+ T cells show similar TCR?? 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 TCR?? clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.

SUBMITTER: Wang Z

PROVIDER: S-EPMC5827521 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Wang Zhongfang Z Zhu Lingyan L Nguyen Thi H O THO Wan Yanmin Y Sant Sneha S Quiñones-Parra Sergio M SM Crawford Jeremy Chase JC Eltahla Auda A AA Rizzetto Simone S Bull Rowena A RA Qiu Chenli C Koutsakos Marios M Clemens E Bridie EB Loh Liyen L Chen Tianyue T Liu Lu L Cao Pengxing P Ren Yanqin Y Kedzierski Lukasz L Kotsimbos Tom T McCaw James M JM La Gruta Nicole L NL Turner Stephen J SJ Cheng Allen C AC Luciani Fabio F Zhang Xiaoyan X Doherty Peter C PC Thomas Paul G PG Xu Jianqing J Kedzierska Katherine K

Nature communications 20180226 1

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 analyse ...[more]

PMID: 29483513

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Project description:BackgroundThe global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection.MethodsA total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3-7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.ResultsWe revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.ConclusionsOur findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.

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

Publications

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

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