Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

• Published in: eLife Vol. 12
• Main Authors: Mijnheer, Gerdien, Servaas, Nila Hendrika, Leong, Jing Yao, Boltjes, Arjan, Spierings, Eric, Chen, Phyllis, Lai, Liyun, Petrelli, Alessandra, Vastert, Sebastiaan, de Boer, Rob J, Albani, Salvatore, Pandit, Aridaman, van Wijk, Femke
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications, Ltd 23.01.2023; eLife Sciences Publications Ltd
• Subjects: Arthritis, Juvenile; Clone Cells; CyTOF; Humans; Immunology and Inflammation; Inflammation; juvenile idiopathic arthritis; Receptors, Antigen, T-Cell; regulatory T cell; t cell receptor; T-Lymphocytes, Regulatory; tissue inflammation; inflammation; t cell receptor; tissue inflammation; regulatory T cell; juvenile idiopathic arthritis; CyTOF; human; immunology
• DOI: 10.7554/eLife.79016
• ISSN: 2050-084X

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 autoantigen-driven expansion of both Teffector and Treg clones that are highly persistent and are (re)circulating. These dominant clones might represent interesting therapeutic targets.