CD4 T cell covid-19 Ziegler et al

Description

Persistent CD4+ T cell functional deficits during recovery from prolonged symptomatic SARS-CoV-2 infection. Symptoms of acute SARS-CoV-2 infection often resolve quickly but are sometimes associated with persistent immune dysfunction. However, the factors that predispose individuals to compromised immune function have not been defined. Herein, we investigated CD4+ T cell phenotype and function in 17 individuals who recovered from mild to moderate SARS-CoV-2 infection without hospitalization and were divided into short or prolonged symptom duration groups. Five individuals with prolonged symptom duration (CD4low group) showed marked downregulation of CD4 on CD3+CD8– T cells and a poor response to TCR stimulation with the superantigen Staphylococcal enterotoxin B (SEB), as shown by weak upregulation of the activation markers CD134 and CD69. CD4 surface intensities recovered to normal levels in four of these individuals within 3-12 months. Selected cytokines (IL-1RA, IL-7, and VEGF) were elevated in individuals with low CD4, but plasma levels of anti-S1 IgG did not correlate with CD4 defects. Bulk RNA sequencing of unstimulated and SEB-treated CD3+CD8– T cells revealed a >50% reduction in the number of differentially expressed genes in the CD4low group compared to the same individuals after CD4 levels were recovered and a healthy control group. Upstream regulator analysis of differentially expressed genes in unstimulated CD4low cells suggested a response to IFN, while SEB-stimulated CD4low cells showed reduced functionality of IL-2, CD28, and SATB1 regulated pathways. In summary, prolonged symptomatic recovery from SARS-CoV-2 infection was associated with a global CD4+ T cell response defect, defined by low surface CD4 expression, evidence of IFN signaling, and defective T cell activation.

Steps to reproduce

PBMC from individuals recovered from SARS-CoV-2 infection (2 time points) and healthy controls were stimulated with SEB (Staphylococcal enterotoxin B) or left unstimulated for 18hr. CD4+ T cells were isolated by flow cytometric sorting and subjected to RNA sequencing. The raw count matrix file is uploaded. 1A subject Covid 4, timepoint 1, NoSEB 1B subject Covid 4, timepoint 1, SEB 12A subject Covid 4, timepoint 2, NoSEB 12B subject Covid 4, timepoint 2, SEB 2A subject Covid 1, timepoint 1, NoSEB 2B subject Covid 1, timepoint 1, SEB 4A subject Covid 1, timepoint 2, NoSEB 4B subject Covid 1, timepoint 2, SEB 3A subject Covid 2, timepoint 1, NoSEB 3B subject Covid 2, timepoint 1, SEB 5A subject Covid 2, timepoint 2, NoSEB 5B subject Covid 2, timepoint 2, SEB 6A subject Covid 8, timepoint 1, NoSEB 6B subject Covid 8, timepoint 1, SEB 9A subject Covid 8, timepoint 2, NoSEB 9B subject Covid 8, timepoint 2, SEB 18A subject Covid 9, timepoint 1, NoSEB 18B subject Covid 9, timepoint 1, SEB 10A subject Covid 9, timepoint 2, NoSEB 10B subject Covid 9, timepoint 2, SEB 13A subject Control 1, timepoint 1, NoSEB 13B subject Control 1, timepoint 1, SEB 14B subject Control 3, timepoint 1, SEB 15A subject Control 4, timepoint 1, NoSEB 15B subject Control 4, timepoint 1, SEB 16A subject Control 8, timepoint 1, NoSEB 16B subject Control 8, timepoint 1, SEB 17A subject Control 12, timepoint 1, NoSEB 17B subject Control 12, timepoint 1, SEB

Institutions

• Oklahoma Medical Research Foundation

  OK, Oklahoma City

Categories

Funders

• National Institutes of Health

  United States Department of Health and Human Services

  Maryland, United States

  Grant ID: 3U19 AI062629-17S2

Licence