High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19
Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4<sup>+</sup> T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/6/1265 |
| _version_ | 1797481399674994688 |
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| author | Leon Cords Maximilian Knapp Robin Woost Sophia Schulte Silke Kummer Christin Ackermann Claudia Beisel Sven Peine Alexandra Märta Johansson William Wai-Hung Kwok Thomas Günther Nicole Fischer Melanie Wittner Marylyn Martina Addo Samuel Huber Julian Schulze zur Wiesch |
| author_facet | Leon Cords Maximilian Knapp Robin Woost Sophia Schulte Silke Kummer Christin Ackermann Claudia Beisel Sven Peine Alexandra Märta Johansson William Wai-Hung Kwok Thomas Günther Nicole Fischer Melanie Wittner Marylyn Martina Addo Samuel Huber Julian Schulze zur Wiesch |
| author_sort | Leon Cords |
| collection | DOAJ |
| description | Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4<sup>+</sup> 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<sup>+</sup> T-cell response in both patients, with higher frequencies of virus-specific CD4<sup>+</sup> T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4<sup>+</sup> 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<sup>+</sup> T-cells with CD45RA<sup>−</sup> CXCR5<sup>+</sup> PD-1<sup>+</sup> circulating T follicular helper cell (cT<sub>FH</sub>) phenotype. Furthermore, we observed a delayed contraction of CD127<sup>−</sup> virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4<sup>+</sup> 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<sup>+</sup> T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection. |
| first_indexed | 2024-03-09T22:14:01Z |
| format | Article |
| id | doaj.art-1e8ef9c65a904696a4ab4d1c8c5d6aa1 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:14:01Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-1e8ef9c65a904696a4ab4d1c8c5d6aa12023-11-23T19:26:29ZengMDPI AGViruses1999-49152022-06-01146126510.3390/v14061265High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19Leon Cords0Maximilian Knapp1Robin Woost2Sophia Schulte3Silke Kummer4Christin Ackermann5Claudia Beisel6Sven Peine7Alexandra Märta Johansson8William Wai-Hung Kwok9Thomas Günther10Nicole Fischer11Melanie Wittner12Marylyn Martina Addo13Samuel Huber14Julian Schulze zur Wiesch15Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyBenaroya Research Institute at Virginia Mason, Seattle, WA 98101, USABenaroya Research Institute at Virginia Mason, Seattle, WA 98101, USALeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, GermanyGerman Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInfectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyHere, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4<sup>+</sup> 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<sup>+</sup> T-cell response in both patients, with higher frequencies of virus-specific CD4<sup>+</sup> T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4<sup>+</sup> 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<sup>+</sup> T-cells with CD45RA<sup>−</sup> CXCR5<sup>+</sup> PD-1<sup>+</sup> circulating T follicular helper cell (cT<sub>FH</sub>) phenotype. Furthermore, we observed a delayed contraction of CD127<sup>−</sup> virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4<sup>+</sup> 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<sup>+</sup> T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection.https://www.mdpi.com/1999-4915/14/6/1265SARS-CoV-2COVID-19CD4<sup>+</sup> T-cellsT-cell memoryMHC class II TetramerPD-1 |
| spellingShingle | Leon Cords Maximilian Knapp Robin Woost Sophia Schulte Silke Kummer Christin Ackermann Claudia Beisel Sven Peine Alexandra Märta Johansson William Wai-Hung Kwok Thomas Günther Nicole Fischer Melanie Wittner Marylyn Martina Addo Samuel Huber Julian Schulze zur Wiesch High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19 Viruses SARS-CoV-2 COVID-19 CD4<sup>+</sup> T-cells T-cell memory MHC class II Tetramer PD-1 |
| title | High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19 |
| title_full | High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19 |
| title_fullStr | High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19 |
| title_full_unstemmed | High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19 |
| title_short | High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4<sup>+</sup> T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19 |
| title_sort | high and sustained ex vivo frequency but altered phenotype of sars cov 2 specific cd4 sup sup t cells in an anti cd20 treated patient with prolonged covid 19 |
| topic | SARS-CoV-2 COVID-19 CD4<sup>+</sup> T-cells T-cell memory MHC class II Tetramer PD-1 |
| url | https://www.mdpi.com/1999-4915/14/6/1265 |
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