Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells

Marie A C Depuydt; Frank H Schaftenaar; Koen H M Prange; Arjan Boltjes; Esmeralda Hemme; Lucie Delfos; Jill de Mol; Maaike J M de Jong; Mireia N A Bernabé Kleijn; Judith A H M Peeters; Lauren Goncalves; Anouk Wezel; Harm J Smeets; Gert J de Borst; Amanda C Foks; Gerard Pasterkamp; Menno P J de Winther; Johan Kuiper; Ilze Bot; Bram Slütter

doi:10.1038/s44161-022-00208-4

Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells

Nat Cardiovasc Res. 2023;2(2):112-125. doi: 10.1038/s44161-022-00208-4. Epub 2023 Jan 30.

Authors

Marie A C Depuydt^#¹, Frank H Schaftenaar^#¹, Koen H M Prange², Arjan Boltjes³, Esmeralda Hemme¹, Lucie Delfos¹, Jill de Mol¹, Maaike J M de Jong¹, Mireia N A Bernabé Kleijn¹, Judith A H M Peeters⁴, Lauren Goncalves⁴, Anouk Wezel⁴, Harm J Smeets⁴, Gert J de Borst⁵, Amanda C Foks¹, Gerard Pasterkamp³, Menno P J de Winther², Johan Kuiper¹, Ilze Bot¹, Bram Slütter¹

Affiliations

¹ Leiden Academic Centre for Drug Research, Division of Biotherapeutics, Leiden University, Leiden, the Netherlands.
² Amsterdam University Medical Centers, University of Amsterdam, Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam, the Netherlands.
³ Central Diagnostic Laboratory, University Medical Center, Utrecht University, Utrecht, the Netherlands.
⁴ Department of Surgery, Haaglanden Medisch Centrum Westeinde, The Hague, the Netherlands.
⁵ Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, the Netherlands.

^# Contributed equally.

Abstract

Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell samples to assess the extent of TCR clonality and antigen-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4⁺ T cells, and these clonally expanded T cells expressed genes such as CD69, FOS and FOSB, indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector CD4⁺ T cells with foam cells. Finally, we integrated a published scTCR-seq dataset of the autoimmune disease psoriatic arthritis, and we report various commonalities between the two diseases. In conclusion, our data suggest that atherosclerosis has an autoimmune compondent driven by autoreactive CD4⁺ T cells.

Keywords: Atherosclerosis; Autoimmunity.