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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 :
- Nat Cardiovasc Res
- Publication Year :
- 2022
- Publisher :
- Springer Science and Business Media LLC, 2022.
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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.
- Subjects :
- Article
Subjects
Details
- ISSN :
- 27310590
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Cardiovascular Research
- Accession number :
- edsair.doi.dedup.....3cd2538a5cbb8e4f12326b27b40c27dd