1. Substantive Similarities Between Synovial Fluid and Synovial Tissue T cells in Inflammatory Arthritis Via Single‐Cell RNA and T Cell Receptor Sequencing.
- Author
-
Durham, Lucy E., Humby, Frances C., Ng, Nora, Ryan, Sarah, Nuamah, Rosamond, Fung, Kathy, Kallayil, Athul Menon, Dhami, Pawan, Kirkham, Bruce W., and Taams, Leonie S.
- Subjects
SYNOVIAL membranes ,T cells ,SYNOVIAL fluid ,RHEUMATOID arthritis ,IMMUNOLOGIC memory ,DESCRIPTIVE statistics ,RNA ,GENE expression ,COMPARATIVE studies ,CELL receptors ,SEQUENCE analysis - Abstract
Objective: Synovial fluid (SF)–derived T cells are frequently studied as a proxy for investigating the synovial tissue (ST) T cell infiltrate in inflammatory arthritis. However, because ST is the primary site of inflammatory activity, there is debate as to whether SF provides a true reflection of the ST T cell population. Methods: In this study, we used single‐cell RNA sequencing paired with single‐cell T cell receptor (TCR) sequencing to directly compare memory T cells from paired samples of SF and ST from six patients with inflammatory arthritis to investigate their similarity in terms of TCR repertoire and T cell subset composition. Results: The TCR repertoires of SF and ST T cells were strikingly similar, particularly for CD8+ T cells. A median of 49% of the total CD8+ TCR repertoire in SF was shared with ST, compared with 20% shared with blood. Similarly, 47% of the ST CD8+ TCR repertoire was shared with SF compared to 25% with blood. Furthermore, once the effect of collagenase digestion on gene expression by ST T cells had been accounted for, the frequencies of specific CD8+ and CD4+ T cell subsets were, in general, similar in SF and ST and were distinct from blood. Conclusion: Our results suggest that T cells migrate and equilibrate between the SF and ST and maintain similar phenotypes in both sites. We conclude that SF is an appropriate proxy for investigating the T cell infiltrate in inflamed synovium, particularly in terms of investigating the TCR repertoire. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF