TREG cells and CXCR3+ circulating TFH cells concordantly shape the neutralizing antibody responses in individuals who have recovered from mild COVID-19

Xingyu Zheng; Rui Lu; Dong Pan; Liting Peng; Rongzhang He; Yabin Hu; Jun Chen; Jinyong Tang; Xiaohan Rong; Shishan Teng; You Wang; Fen Liu; Tianyi Xie; Chanfeng Wu; Yinggen Tang; Wenpei Liu; Xiaowang Qu

doi:10.1093/infdis/jiae061

TREG cells and CXCR3+ circulating TFH cells concordantly shape the neutralizing antibody responses in individuals who have recovered from mild COVID-19

J Infect Dis. 2024 Feb 7:jiae061. doi: 10.1093/infdis/jiae061. Online ahead of print.

Authors

Xingyu Zheng^{1

2}, Rui Lu^{1

2}, Dong Pan^{1

2}, Liting Peng^{1

2}, Rongzhang He², Yabin Hu², Jun Chen², Jinyong Tang², Xiaohan Rong², Shishan Teng², You Wang^{2

3}, Fen Liu^{1

2}, Tianyi Xie^{1

2}, Chanfeng Wu^{1

2}, Yinggen Tang^{2

3}, Wenpei Liu¹, Xiaowang Qu¹

Affiliations

¹ College of Basic Medicine, Hengyang Medical School, University of South China & MOE Key Lab of Rare Paediatric Diseases, Hengyang 421001, China.
² Translational Medicine Institute, The First People's Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou 423000, China.
³ School of Public Health, University of South China, Hengyang 421001, China.

PMID: 38324762
DOI: 10.1093/infdis/jiae061

Abstract

Regulatory T (TREG) cells are involved in the antiviral immune response in patients with 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 TFH (cTFH) cells than healthy controls. Furthermore, 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 a 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.