IL-6 drives T cell death to participate in lymphopenia in COVID-19

https://doi.org/10.1016/j.intimp.2022.109132Get rights and content

Highlights

  • CD4+ T cell reduction, a reliable indicator of severity and hospitalization in COVID-19 patients.

  • Exposure to IL-1β, IL-6, TNF-α and IFN-γ of COVID-19 cytokine storm caused activated T cells substantial death.

  • IL-6 induced gasderminE-mediated pyroptosis of T cells.

Abstract

Lymphopenia is a common observation in patients with COVID-19. To explore the cause of T cell lymphopenia in the disease, laboratory results of 64 hospitalized COVID-19 patients were retrospectively analyzed and six patients were randomly selected to trace their changes of T lymphocytes and plasma concentration of IL-6 for the course of disease. Results confirmed that the T-cell lymphopenia, especially CD4+ T cell reduction in COVID-19 patients, was a reliable indicator of severity and hospitalization in infected patients. And CD4+ T cell count below 200 cells/μL predicts critical illness in COVID-19 patients. In vitro assay supported that exposure to key contributors (IL-1β, IL-6, TNF-α and IFN-γ) of COVID-19 cytokine storm caused substantial death of activated T cells. Among these contributors, IL-6 level was found to probably reversely correlate with T cell counts in patients. And IL-6 alone was potent to induce T cell reduction by gasderminE-mediated pyroptosis, inferring IL-6 took a part in affecting the function and status of T cells in COVID-19 patients. Intervention of IL-6 mediated T cell pryprotosis may effectively delay disease progression, maintain normal immune status at an early stage of infection.

Keywords

Lymphopenia
COVID-19
IL-6
SARS-CoV-2
ICU care

Abbreviations

COVID-19
coronavirus disease 2019
ICU
intensive care unit
OR
odds ratio
CI
confidence interval. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
CKs
cytokine mixture

Data availability

Data will be made available on request.

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1

These authors contributed equally to this work.

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