Tu158 - TNFα-producing CD4+ T Cells Dominate the SARS-CoV-2-specific T Cell Response in COVID-19 Outpatients and are Associated with Durable Antibodies

Tuesday, June 21, 2022

6:15 PM – 7:45 PM PT

Presenting Author(s)

Kv

Kattria van Der Ploeg, PhD

Postdoctoral Researcher
Stanford University
Palo Alto, California, United States

Co-Author(s)

AK

Adam Kirosingh, B.Sc.

Stanford University
Palo Alto, California, United States
DM

Diego Mori, B.Sc.

Stanford University
Palo Alto, California, United States
SC

Saborni Chakraborty, n/a

Stanford University
Stanford, California, United States
Zicheng Hu, PhD

Researcher
University of California at San Francisco
San Francisco, California, United States
BS

Benjamin Seivers, BA

J. Craig Venter Institute
La Jolla, California, United States
KJ

Karen Jacobson, MD

Stanford University
Palo Alto, California, United States
HB

Hector Bonilla, MD

Stanford University
Palo Alto, California, United States
JP

Julie Parsonnet, MD

Stanford University
Palo Alto, California, United States
JA

Jason R. Andrews, MD

Stanford University
Palo Alto, California, United States
KP

Kathleen D. Press, PhD

Postdoctoral fellow
Stanford School of Medicine
Stanford, California, United States
MT

Maureen Ty, PhD

Stanford University
Palo Alto, California, United States
DR

Daniel Ruiz-Betancourt, B.Sc.

Stanford University
Palo Alto, California, United States
Ld

Lauren de la Parte, B.Sc.

Stanford University
Palo Alto, California, United States
GT

Gene Tan, PhD

J. Craig Venter Institute
La Jolla, California, United States
CB

Catherine Blish, PhD

Stanford University
Palo Alto, California, United States
ST

Saki Takahashi, PhD

University of California, San Francisco
San Francisco, California, United States
IR

Isabel Rodriguez-Barraquer, MD, PhD

University of California, San Francisco
San Francisco, California, United States
BG

Bryan Greenhouse, MD

University of California at San Francisco
San Francisco, California, United States
US

Upinder Singh, MD

Stanford University
Palo Alto, California, United States
TW

Taia T. Wang, n/a

Stanford University
Stanford, California, United States
PJ

Prasanna Jagannathan, MD

Stanford School of Medicine
Stanford, California, United States

SARS-CoV-2-specific CD4+ T cells are likely important in immunity against COVID-19, but our understanding of CD4+ longitudinal dynamics following infection, and specific features that correlate with the maintenance of neutralizing antibodies, remains limited. We characterized SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients. We observed that the quality of the SARS-CoV-2-specific CD4+ response shifted from cells producing IFNγ to TNFα from five days to four months post-enrollment, with IFNγ-IL21-TNFα+ CD4+ T cells the predominant population detected at later timepoints. These IFNγ-IL21-TNFα+ cells highly correlated with activation induced marker (AIM)+ CD4+ T cell populations, including ICOS+ circulating T follicular helper cells (cTfh). Greater percentages of IFNγ-IL21-TNFα+ CD4+ T cells on day 28 correlated with SARS-CoV-2 neutralizing antibodies measured seven months post-infection (⍴=0.4, P=0.01). Similar positive correlations were observed with activated ICOS+ cTfh and neutralizing antibodies. mRNA vaccination following SARS-CoV-2 infection boosted both IFNγ and TNFα producing, spike protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNFα-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.