Imbalance of SARS-CoV-2-specific CCR6+ and CXCR3+ CD4+ T cells and IFN-γ + CD8+ T cells in patients with Long-COVID

Clin Immunol. 2024 Jul:264:110267. doi: 10.1016/j.clim.2024.110267. Epub 2024 May 31.

Abstract

Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4+ cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8+ T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6+ CD4+ subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6+ CD4+ are decreased in LC patients, whereas CXCR3+ CCR6- and CCR4+ CCR6- CD4+ T cells are increased. LC patients showed lower IFN-γ-secreting CD8+ T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC.

Keywords: COVID-19; Chemokine receptors; IFN-γ; Long-COVID; T cells.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • COVID-19* / immunology
  • Female
  • Humans
  • Interferon-gamma* / immunology
  • Interferon-gamma* / metabolism
  • Male
  • Middle Aged
  • Receptors, CCR6* / immunology
  • Receptors, CCR6* / metabolism
  • Receptors, CXCR3* / immunology
  • Receptors, CXCR3* / metabolism
  • SARS-CoV-2* / immunology

Substances

  • Receptors, CCR6
  • Receptors, CXCR3
  • Interferon-gamma
  • CCR6 protein, human
  • CXCR3 protein, human