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Beck, F.* ; Nguyen, P.* ; Hoffmann, A. ; Loyal, L.* ; Thiel, A.* ; Melzer, M.* ; Apel, H.* ; Pierer, M.* ; Krasselt, M.* ; Seifert, O.* ; Glimm, A.M.* ; Hagemann, T. ; Rothe, K.* ; Wagner, U.*

CD4+CD8αlow T cells in rheumatoid arthritis are clonally expanded and dependent on co-stimulation.

Arthritis Rheum., DOI: 10.1002/art.42960 (2024)
DOI PMC
: Postprint online verfügbar 07/2025
OBJECTIVES: CD4+CD8+ T cells are increased in patients with rheumatoid arthritis (RA). They are not only associated with joint erosions in established disease, but are also present in the pre-clinical stages of RA. This study aims to further investigate their expansion in the context of T cell clonality in patients with RA, as well as their responsiveness to T cell targeted treatment. METHODS: Single-cell-(sc)RNA- and scTCR-sequencing data were used to determine co-receptor expression and T cell receptor sequences to assess clonality of CD4+CD8+ T cells in RA (n=3) patients and healthy controls (n=2). Peripheral CD4+CD8+ T cells and their subpopulations were measured in patients with RA (n=53), PsA (n=52) and healthy donors (n=50) using flow cytometry. In addition, changes in CD4+CD8+ T cell frequency were prospectively followed in RA patients receiving therapy with abatacept for 12 weeks. RESULTS: We observed an increase of CD4+ T cells expressing CD8α in RA patients, both in comparison to PsA patients and to healthy controls. Clonality analysis revealed, that these CD4+CD8αlow T cells are part of large T cell clones, which cluster separately from CD4+CD8- T cell clones in the scRNA-seq gene expression analysis. Treatment with abatacept significantly reduced the frequency of peripheral CD4+CD8αlow T cells, and this was linked to reduction in disease activity. CONCLUSION: In RA, clonal expansion of CD4+ T cell clones culminates in the emergence of peripheral CD4+CD8αlow T cells, which are associated with disease activity and diminished upon abatacept treatment, and which could contribute to disease pathogenesis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 0004-3591
e-ISSN 1529-0131
Zeitschrift Arthritis & Rheumatology
Verlag Wiley
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)