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
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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. / Cords, Leon; Knapp, Maximilian; Woost, Robin; Schulte, Sophia; Kummer, Silke; Ackermann, Christin; Beisel, Claudia; Peine, Sven; Johansson, Alexandra Märta; Kwok, William Wai-Hung; Günther, Thomas; Fischer, Nicole; Wittner, Melanie; Addo, Marylyn Martina; Huber, Samuel; Schulze Zur Wiesch, Julian.
in: VIRUSES-BASEL, Jahrgang 14, Nr. 6, 1265, 10.06.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - 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
AU - Cords, Leon
AU - Knapp, Maximilian
AU - Woost, Robin
AU - Schulte, Sophia
AU - Kummer, Silke
AU - Ackermann, Christin
AU - Beisel, Claudia
AU - Peine, Sven
AU - Johansson, Alexandra Märta
AU - Kwok, William Wai-Hung
AU - Günther, Thomas
AU - Fischer, Nicole
AU - Wittner, Melanie
AU - Addo, Marylyn Martina
AU - Huber, Samuel
AU - Schulze Zur Wiesch, Julian
PY - 2022/6/10
Y1 - 2022/6/10
N2 - 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 (cTFH) 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.
AB - 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 (cTFH) 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.
KW - CD4-Positive T-Lymphocytes
KW - COVID-19
KW - Humans
KW - Phenotype
KW - SARS-CoV-2
KW - T-Lymphocytes, Helper-Inducer
U2 - 10.3390/v14061265
DO - 10.3390/v14061265
M3 - SCORING: Journal article
C2 - 35746736
VL - 14
JO - VIRUSES-BASEL
JF - VIRUSES-BASEL
SN - 1999-4915
IS - 6
M1 - 1265
ER -