Regulatory T and CXCR3+ Circulating Tfh Cells Concordantly Shape the Neutralizing Antibody Responses in Individuals Who Have Recovered from Mild COVID-19

J Infect Dis. 2024 Jul 25;230(1):28-37. doi: 10.1093/infdis/jiae061.

Abstract

Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.

Keywords: COVID-19; circulating T-follicular helper cell; neutralizing antibody; regulatory T cell.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • COVID-19* / immunology
  • Female
  • Humans
  • Male
  • Memory B Cells / immunology
  • Middle Aged
  • Receptors, CXCR3* / immunology
  • Receptors, CXCR3* / metabolism
  • T Follicular Helper Cells* / immunology
  • T-Lymphocytes, Regulatory* / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • CXCR3 protein, human
  • Receptors, CXCR3