학술논문
TNF-α+ CD4+ T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies
Document Type
article
Author
van der Ploeg, Kattria; Kirosingh, Adam S; Mori, Diego AM; Chakraborty, Saborni; Hu, Zicheng; Sievers, Benjamin L; Jacobson, Karen B; Bonilla, Hector; Parsonnet, Julie; Andrews, Jason R; Press, Kathleen D; Ty, Maureen C; Ruiz-Betancourt, Daniel R; de la Parte, Lauren; Tan, Gene S; Blish, Catherine A; Takahashi, Saki; Rodriguez-Barraquer, Isabel; Greenhouse, Bryan; Singh, Upinder; Wang, Taia T; Jagannathan, Prasanna
Source
Cell Reports Medicine. 3(6)
Subject
Language
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4+ T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4+ longitudinal dynamics following infection and of specific features that correlate with the maintenance of neutralizing antibodies remains limited. Here, we characterize SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4+ response shifts from cells producing interferon gamma (IFNγ) to tumor necrosis factor alpha (TNF-α) from 5 days to 4 months post-enrollment, with IFNγ-IL-21-TNF-α+ CD4+ T cells the predominant population detected at later time points. Greater percentages of IFNγ-IL-21-TNF-α+ CD4+ T cells on day 28 correlate with SARS-CoV-2-neutralizing antibodies measured 7 months post-infection (⍴ = 0.4, p = 0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ- and TNF-α-producing, spike-protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.