Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.735125
Keywords
COVID-19; HLA-DR; CD38; severity; immune disorder
Categories
Funding
- National Natural Science Foundation of China [81971307]
- Beijing Natural Science Foundation [M21007]
- Beijing Municipal Science & Technology Commission [Z201100007920017]
- National Key Sci-Tech Special Project of China [2018ZX10302207]
- National Key Research and Development Program of China [2020YFC0846200]
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The study revealed that HLA-DR(+)CD38(hi) CD8(+) T cells were persistently accumulated in severe COVID-19 patients, showing overactivation and dysregulation, and were associated with systemic inflammation, tissue injury, and immune disorders.
Background The 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. Methods A 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. Results We revealed that the HLA-DR(+)CD38(+) CD8(+) T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR(+)CD38(dim) and HLA-DR(+)CD38(hi). We observed a persistent accumulation of HLA-DR(+)CD38hi CD8(+) T cells in severe COVID-19 patients. These HLA-DR(+)CD38(hi) 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(+)CD38(dim) CD8(+) T cells. Moreover, the clinical and laboratory data supported that only HLA-DR(+)CD38(hi) CD8(+) T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients. Conclusions Our findings indicated that HLA-DR(+)CD38(hi) CD8(+) T cells were correlated with disease severity of COVID-19 rather than HLA-DR(+)CD38(dim) population.
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