Abstract
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.
Keywords: CD39; CD4+ T-cells; CD73; COVID-19; MHC class II Tetramer; PD-1; SARS-CoV-2; T-cell memory; TIGIT; anti-CD20 therapy.
【저자키워드】 COVID-19, SARS-CoV-2, PD-1, CD39, T-cell memory, CD4+ T-cells, CD73, MHC class II Tetramer, TIGIT, anti-CD20 therapy., 【초록키워드】 IL-6, T-cell Response, T-cells, Infection, CRP, CD4, anti-CD20 therapy, memory, PD-1, viral replication, membrane protein, Patient, phenotype, MHC class II, receptor, T-cell, epitope, expression, patients, anti-CD20, B-cell, Interaction, Frequency, Analysis, CD73, TIGIT, T follicular helper cell, helper cell, Ex vivo, help, CD4+, CXCR5, circulating, CD45, CD45RA, effector cells, tetramer, MHC class, LAG-3, Cell, robust, lack, the patient, reduced, abrogate, follicular, inflammation marker, skewed, 【제목키워드】 CD4, Prolonged, Altered,