Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis
- University Medical Center Utrecht, Netherlands
- SingHealth Duke-NUS Academic Medical Centre, Singapore
- Utrecht University, Netherlands
Abstract
Autoimmune inflammation is characterized by tissue infiltration and expansion of antigen-specific T cells. Although this inflammation is often limited to specific target tissues, it remains yet to be explored whether distinct affected sites are infiltrated with the same, persistent T cell clones. Here we performed CyTOF analysis and T cell receptor (TCR) sequencing to study immune cell composition and (hyper-)expansion of circulating and joint-derived Tregs and non-Tregs in Juvenile Idiopathic Arthritis (JIA). We studied different joints affected at the same time, as well as over the course of relapsing-remitting disease. We found that the composition and functional characteristics of immune infiltrates are strikingly similar between joints within one patient, and observed a strong overlap between dominant T cell clones, especially Treg, of which some could also be detected in circulation and persisted over the course of relapsing remitting disease. Moreover, these T cell clones were characterized by a high degree of sequence similarity, indicating the presence of TCR clusters responding to the same antigens. These data suggest that in localized autoimmune disease there is auto-antigen driven expansion of both Teffector and Treg clones, that are highly persistent and are (re)circulating. These dominant clones might represent interesting therapeutic targets.
Data availability
TCR-sequencing data presented in this study have been deposited in NCBI's Gene Expression Omnibus (GEO) database under GSE196301. Both raw data and processed data are available.
Article and author information
Author details
Nila Hendrika Servaas
Funding
ZonMw (91714332)
- Femke van Wijk
Netherlands Organisation for Scientific Research (016.Veni.178.027)
- Aridaman Pandit
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Di Chen, Chinese Academy of Sciences, China
Ethics
Human subjects: Informed consent was obtained from all patients either directly or from parents/guardians when the patients were younger than 12 years of age. The study was conducted in accordance with the Institutional Review Board of the University Medical Center Utrecht (approval no. 11-499/C), in compliance with the Declaration of Helsinki.
Version history
- Preprint posted: February 10, 2022 (view preprint)
- Received: March 29, 2022
- Accepted: January 20, 2023
- Accepted Manuscript published: January 23, 2023 (version 1)
- Version of Record published: March 8, 2023 (version 2)
Copyright
© 2023, Mijnheer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis
eLife 12:e79016.
https://doi.org/10.7554/eLife.79016
Further reading
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