4.6 Article

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Journal

VIRUSES-BASEL
Volume 14, Issue 6, Pages -

Publisher

MDPI
DOI: 10.3390/v14061265

Keywords

SARS-CoV-2; COVID-19; CD4(+) T-cells; T-cell memory; MHC class II Tetramer; PD-1; TIGIT; anti-CD20 therapy; CD39; CD73

Categories

Funding

  1. Deutsches Zentrum fur Infektionsforschung (DZIF) [TTU 04.816]
  2. Deutsche Forschungsgemeinschaft (DFG) [SFB1328 A12, SFB841 A6]
  3. NIH NIDDK [3U19AI135817-04S1]

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This study longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2-specific CD4(+) T-cells in an anti-CD20-treated patient and an immunocompetent patient. The results showed a high and stable CD4(+) T-cell response in both patients, with higher frequencies in the B-cell-depleted patient. However, the B-cell-depleted patient had an altered CD4(+) T-cell phenotype and weaker antiviral effect.
Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145-164) epitope-specific CD4(+) T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We detected a high and stable SARS-CoV-2 membrane-specific CD4(+) T-cell response in both patients, with higher frequencies of virus-specific CD4(+) T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4(+) T-cell memory phenotype in the B-cell-depleted patient that was skewed towards late differentiated memory T-cells, as well as reduced frequencies of SARS-CoV-2-specific CD4(+) T-cells with CD45RA(-) CXCR5(+) PD-1(+) circulating T follicular helper cell (cT(FH)) phenotype. Furthermore, we observed a delayed contraction of CD127(-) virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4(+) T-cells of the patient, but were associated with the inflammation markers IL-6 and CRP. Our findings indicate that, despite B-cell depletion and a lack of B-cell-T-cell interaction, a robust virus-specific CD4(+) T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection.

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