Mucosal-associated invariant T cell responses differ by sex in COVID-19

Abstract

Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.

Broadly directed SARS-CoV-2-specific CD4+ T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19

“…These two peptides are located within the N-terminal domain of the protein [ 24 ]. A number of epitopes described in the current study, have previously been reported ( Table 5 ) [ 15 , 25 – 28 ]. The RF from the respective previous reports as well as the HLA restriction are shown.…”

“…To date, most studies have utilized pools of predicted peptides or pools of overlapping peptides spanning entire antigens, to probe responses to different SARS-CoV-2 antigens [ 3 , 7 – 9 , 12 – 14 ]. However, the exact T cell epitopes and immunodominant antigen regions have only been determined in few studies [ 15 , 25 – 27 ]. Notably, these studies have overall reported a similar response pattern ( Table 5 ), suggesting a reproducibility despite differences in the patient cohorts and methodologies.…”

“…However, the relative role of neutralizing antibodies and T cell responses for protection against symptomatic reinfection has not been defined for SARS-CoV-2. Of note, immunodominant regions priming virus-specific CD4+ T cells were reported to have minimal overlap with antibody epitopes [ 25 ].…”

CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy

“…To further profile CD7 – T cells, we explored publicly available single-cell RNA sequencing (RNA-seq) data sets of healthy donor PBMCs ( 9 – 11 ). We found that CD7 transcript levels in T cells (defined as cells expressing TRAC and CD3E ) in younger individuals (6–16 years) were significantly higher than older individuals (approximately 20–80 years), while T cells from supercentenarians (>110 years) had much lower expression of CD7 than the other 2 age cohorts ( Supplemental Figure 1B ).…”

How to Prepare Spectral Flow Cytometry Datasets for High Dimensional Data Analysis: A Practical Workflow

“…The second data set used was downloaded from Flow Repository, FR-FCM-Z3WR. This study was performed in the context of Covid-19 research and included a 36-color spectral flow cytometry panel (20). Only the healthy controls of this study were included for the pipeline demonstration.…”