Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals
Fang Gong, … , Di Yu, Pengcheng Zhou
Fang Gong, … , Di Yu, Pengcheng Zhou
Published August 25, 2020
Citation Information: J Clin Invest. 2020;130(12):6588-6599. https://doi.org/10.1172/JCI141054.
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Clinical Medicine COVID-19 Immunology

Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals

Abstract

BACKGROUND Marked progress is achieved in understanding the physiopathology of coronavirus disease 2019 (COVID-19), which caused a global pandemic. However, the CD4+ T cell population critical for antibody response in COVID-19 is poorly understood.METHODS In this study, we provided a comprehensive analysis of peripheral CD4+ T cells from 13 COVID-19 convalescent patients, defined as confirmed free of SARS-CoV-2 for 2 to 4 weeks, using flow cytometry and magnetic chemiluminescence enzyme antibody immunoassay. The data were correlated with clinical characteristics.RESULTS We observed that, relative to healthy individuals, convalescent patients displayed an altered peripheral CD4+ T cell spectrum. Specifically, consistent with other viral infections, cTfh1 cells associated with SARS-CoV-2–targeting antibodies were found in COVID-19 covalescent patients. Individuals with severe disease showed higher frequencies of Tem and Tfh-em cells but lower frequencies of Tcm, Tfh-cm, Tfr, and Tnaive cells, compared with healthy individuals and patients with mild and moderate disease. Interestingly, a higher frequency of cTfh-em cells correlated with a lower blood oxygen level, recorded at the time of admission, in convalescent patients. These observations might constitute residual effects by which COVID-19 can impact the homeostasis of CD4+ T cells in the long-term and explain the highest ratio of class-switched virus-specific antibody producing individuals found in our severe COVID-19 cohort.CONCLUSION Our study demonstrated a close connection between CD4+ T cells and antibody production in COVID-19 convalescent patients.FUNDING Six Talent Peaks Project in Jiangsu Province and the National Natural Science Foundation of China (NSFC).

Authors

Fang Gong, Yaping Dai, Ting Zheng, Liang Cheng, Dan Zhao, Hao Wang, Min Liu, Hao Pei, Tengchuan Jin, Di Yu, Pengcheng Zhou

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Figure 1

Peripheral CD4+ T cell subsets in COVID-19 convalescent patients.

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Peripheral CD4+ T cell subsets in COVID-19 convalescent patients. Blood ...
Blood samples were collected from COVID-19 convalescent patients (n = 13) and healthy individuals (n = 13). PBMCs were isolated for antibody staining and FACs phenotyping of CD4+ T cells. (A) Gating strategies on naive CD4+ T cells (CD45RA+CCR7+), central-memory CD4+ T cells (CD45RA–CCR7+), and effector-memory CD4+ T cells (CD45RA–CCR7–). (B) Statistical analysis of the frequency of CD4+ Tnaive, CD4+ Tcm, and CD4+ Tem cells between healthy individuals and COVID-19 convalescent patients. (C) Gating strategies on different peripheral circulating CD4+ T cell subsets, including CD25–CD45RA–CXCR5+ cTfh cells, CCR7hiPD-1– central-memory cTfh (cTfh-cm) cells, CCR7loPD-1+ effector-memory cTfh (cTfh-em) cells, CXCR3+CCR6– cTfh (cTfh1) cells, CXCR3–CCR6– cTfh (cTfh2) cells, and CXCR3–CCR6+ cTfh (cTfh17) cells. Within CD3+CD8–CD4+ circulating T cells, Th1 cells were defined as CD25–CD45RA–CXCR3+CCR6– cells, Th2 cells as CD25–CD45RA–CXCR3–CCR6– cells, and Th17 cells as CD25–CD45RA–CXCR3–CCR6+ cells. Circulating Treg cells were defined as CD25+CD45RA–CD127– cells and cTfr cells as CD25+CD45RA–CD127–CXCR5hiPD-1hi cells. (D) FACs plot showing the representative cTfh-cm and cTfh-em cells between healthy individuals and COVID-19 convalescent patients. Quantifications on the frequency of these cells within cTfh cells (E) and CD4+ T cells (F). (G) Frequency of cTfh1, cTfh2, and cTfh17 cells within cTfh cells in healthy individuals and COVID-19 convalescent patients. (H) Statistical analysis showing the differences of the frequencies of Treg and cTfr cells between healthy individuals and COVID-19 convalescent patients, and the same analysis on Th1, Th2, and Th17 cells (I). (J) Histogram showing the PD-1 expression on Th1, Th2, and Th17 cells between healthy individuals and COVID-19 convalescent patients. HC, healthy control individuals (n = 13); CP, COVID-19 convalescent patients (n = 13). Each dot represents an individual subject. Bars represent the mean values. *P < 0.05 and **P < 0.01 by unpaired and 2-tailed Student’s t test.