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Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease.
- Source :
-
Nature cardiovascular research [Nat Cardiovasc Res] 2022 May; Vol. 1 (5), pp. 462-475. Date of Electronic Publication: 2022 May 12. - Publication Year :
- 2022
-
Abstract
- Atherosclerosis is accompanied by a CD4 T cell response to apolipoprotein B (APOB). Major Histocompatibility Complex (MHC)-II tetramers can be used to isolate antigen-specific CD4 T cells by flow sorting. Here, we produce, validate and use an MHC-II tetramer, DRB1*07:01 APOB-p18, to sort APOB-p18-specific cells from peripheral blood mononuclear cell samples from 8 DRB1*07:01+ women with and without subclinical cardiovascular disease (sCVD). Single cell RNA sequencing showed that transcriptomes of tetramer+ cells were between regulatory and memory T cells in healthy women and moved closer to memory T cells in women with sCVD. TCR sequencing of tetramer+ cells showed clonal expansion and V and J segment usage similar to those found in regulatory T cells. These findings suggest that APOB-specific regulatory T cells may switch to a more memory-like phenotype in women with atherosclerosis. Mouse studies showed that such switched cells promote atherosclerosis.<br />Competing Interests: DISCLOSURES There are no conflicts of interest.
Details
- Language :
- English
- ISSN :
- 2731-0590
- Volume :
- 1
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nature cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 35990517
- Full Text :
- https://doi.org/10.1038/s44161-022-00063-3