Dataset Information

Persistent High Percentage of HLA-DR⁺CD38^high CD8⁺ T Cells Associated With Immune Disorder and Disease Severity of COVID-19.

ABSTRACT:

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.

SUBMITTER: Du J

PROVIDER: S-EPMC8458852 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.MethodsWe adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9-/- mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.ResultsScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.ConclusionsThis study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

Dataset Information

Persistent High Percentage of HLA-DR⁺CD38^high CD8⁺ T Cells Associated With Immune Disorder and Disease Severity of COVID-19.

Background

Methods

Results

Conclusions

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Dataset Information

Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Persistent High Percentage of HLA-DR⁺CD38^high CD8⁺ T Cells Associated With Immune Disorder and Disease Severity of COVID-19.