CD4 + CD8α low T cells in rheumatoid arthritis are clonally expanded and dependent on co-stimulation.

Autor: Beck F; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Nguyen P; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Hoffmann A; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany., Loyal L; Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Immunomics - Regenerative Immunology and Aging, Berlin, Germany.; Si-M / 'Der Simulierte Mensch' a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin; Berlin, Germany., Thiel A; Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Immunomics - Regenerative Immunology and Aging, Berlin, Germany.; Si-M / 'Der Simulierte Mensch' a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin; Berlin, Germany., Melzer M; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Apel H; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Pierer M; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Krasselt M; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Seifert O; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Glimm AM; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Hagemann T; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany., Rothe K; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany., Wagner U; Department of Rheumatology, Medizinische Klinik III, Universität Leipzig, Medizinische Fakultät, Leipzig, Germany.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2024 Jul 25. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1002/art.42960
Abstrakt: 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 + CD8α low 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 + CD8α low 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 + CD8α low T cells, which are associated with disease activity and diminished upon abatacept treatment, and which could contribute to disease pathogenesis.
(This article is protected by copyright. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: