tetano
Editor, Senior Moderator
Cell Rep Med
. 2022 May 3;100640.
doi: 10.1016/j.xcrm.2022.100640. Online ahead of print.
TNF-α [SUP]+[/SUP] CD4 [SUP]+[/SUP] T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies
Kattria van der Ploeg[SUP] 1 [/SUP], Adam S Kirosingh[SUP] 2 [/SUP], Diego A M Mori[SUP] 1 [/SUP], Saborni Chakraborty[SUP] 1 [/SUP], Zicheng Hu[SUP] 3 [/SUP], Benjamin L Sievers[SUP] 4 [/SUP], Karen B Jacobson[SUP] 1 [/SUP], Hector Bonilla[SUP] 1 [/SUP], Julie Parsonnet[SUP] 5 [/SUP], Jason R Andrews[SUP] 1 [/SUP], Kathleen D Press[SUP] 1 [/SUP], Maureen C Ty[SUP] 1 [/SUP], Daniel R Ruiz-Betancourt[SUP] 1 [/SUP], Lauren de la Parte[SUP] 1 [/SUP], Gene S Tan[SUP] 6 [/SUP], Catherine A Blish[SUP] 7 [/SUP], Saki Takahashi[SUP] 8 [/SUP], Isabel Rodriguez-Barraquer[SUP] 8 [/SUP], Bryan Greenhouse[SUP] 9 [/SUP], Upinder Singh[SUP] 10 [/SUP], Taia T Wang[SUP] 10 [/SUP], Prasanna Jagannathan[SUP] 11 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4[SUP]+[/SUP] T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4[SUP]+[/SUP] 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[SUP]-[/SUP]IL-21[SUP]-[/SUP]TNF-α[SUP]+[/SUP] CD4[SUP]+[/SUP] T cells the predominant population detected at later time points. Greater percentages of IFNγ[SUP]-[/SUP]IL-21[SUP]-[/SUP]TNF-α[SUP]+[/SUP] CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4[SUP]+[/SUP] T cells may play an important role in antibody maintenance following COVID-19.
Keywords: CD4; COVID-19; SARS-CoV-2; T cells; TNF-α; Tfh; antibodies; cytokines; longitudinal; neutralizing antibodies.
. 2022 May 3;100640.
doi: 10.1016/j.xcrm.2022.100640. Online ahead of print.
TNF-α [SUP]+[/SUP] CD4 [SUP]+[/SUP] T cells dominate the SARS-CoV-2 specific T cell response in COVID-19 outpatients and are associated with durable antibodies
Kattria van der Ploeg[SUP] 1 [/SUP], Adam S Kirosingh[SUP] 2 [/SUP], Diego A M Mori[SUP] 1 [/SUP], Saborni Chakraborty[SUP] 1 [/SUP], Zicheng Hu[SUP] 3 [/SUP], Benjamin L Sievers[SUP] 4 [/SUP], Karen B Jacobson[SUP] 1 [/SUP], Hector Bonilla[SUP] 1 [/SUP], Julie Parsonnet[SUP] 5 [/SUP], Jason R Andrews[SUP] 1 [/SUP], Kathleen D Press[SUP] 1 [/SUP], Maureen C Ty[SUP] 1 [/SUP], Daniel R Ruiz-Betancourt[SUP] 1 [/SUP], Lauren de la Parte[SUP] 1 [/SUP], Gene S Tan[SUP] 6 [/SUP], Catherine A Blish[SUP] 7 [/SUP], Saki Takahashi[SUP] 8 [/SUP], Isabel Rodriguez-Barraquer[SUP] 8 [/SUP], Bryan Greenhouse[SUP] 9 [/SUP], Upinder Singh[SUP] 10 [/SUP], Taia T Wang[SUP] 10 [/SUP], Prasanna Jagannathan[SUP] 11 [/SUP]
Affiliations
- PMID: 35588734
- PMCID: PMC9061140
- DOI: 10.1016/j.xcrm.2022.100640
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4[SUP]+[/SUP] T cells are likely important in immunity against coronavirus 2019 (COVID-19), but our understanding of CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4[SUP]+[/SUP] 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[SUP]-[/SUP]IL-21[SUP]-[/SUP]TNF-α[SUP]+[/SUP] CD4[SUP]+[/SUP] T cells the predominant population detected at later time points. Greater percentages of IFNγ[SUP]-[/SUP]IL-21[SUP]-[/SUP]TNF-α[SUP]+[/SUP] CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cells. These data suggest that SARS-CoV-2-specific, TNF-α-producing CD4[SUP]+[/SUP] T cells may play an important role in antibody maintenance following COVID-19.
Keywords: CD4; COVID-19; SARS-CoV-2; T cells; TNF-α; Tfh; antibodies; cytokines; longitudinal; neutralizing antibodies.