CD4 ⁺ CD8α ^low T Cell Clonal Expansion Dependent on Costimulation in Patients With Rheumatoid Arthritis.

Publisher: Wiley Country of Publication: United States NLM ID: 101623795 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-5205 (Electronic) Linking ISSN: 23265191 NLM ISO Abbreviation: Arthritis Rheumatol Subsets: MEDLINE

Original Publication: Malden, MA : Wiley, [2014]-

Arthritis, Rheumatoid*/immunology ; Arthritis, Rheumatoid*/drug therapy ; Arthritis, Rheumatoid*/genetics ; Abatacept*/therapeutic use ; Abatacept*/pharmacology ; CD4-Positive T-Lymphocytes*/immunology ; CD8-Positive T-Lymphocytes*/immunology ; Antirheumatic Agents*/therapeutic use ; Antirheumatic Agents*/pharmacology ; Arthritis, Psoriatic*/immunology ; Arthritis, Psoriatic*/drug therapy; Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Receptors, Antigen, T-Cell/immunology ; Case-Control Studies

Objective: 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 preclinical 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 RNA (scRNA) and single-cell T cell receptor (TCR) sequencing data were used to determine coreceptor expression and TCR sequences to assess the clonality of CD4 ⁺ CD8 ⁺ T cells in patients with RA (n = 3) and healthy controls (n = 2). Peripheral CD4 ⁺ CD8 ⁺ T cells and their subpopulations were measured in patients with RA (n = 53), patients with psoriatic arthritis (PsA; n = 52), and healthy donors (n = 50) using flow cytometry. In addition, changes in CD4 ⁺ CD8 ⁺ T cell frequency were prospectively observed in patients with RA receiving therapy with abatacept for 12 weeks.
Results: We observed an increase of CD4 ⁺ T cells expressing CD8α in patients with RA, both in comparison to patients with PsA and 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 sequencing (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 patients with RA, clonal expansion of CD4 ⁺ T cell culminates in the emergence of peripheral CD4 ⁺ CD8α ^low T cells, which are associated with disease activity and diminished upon abatacept treatment and could contribute to disease pathogenesis.
(© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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WA 2765/13 Deutsche Forschungsgemeinschaft (DFG); WA 2765/5 Deutsche Forschungsgemeinschaft (DFG)

7D0YB67S97 (Abatacept)
0 (Antirheumatic Agents)
0 (Receptors, Antigen, T-Cell)

Date Created: 20240726 Date Completed: 20241129 Latest Revision: 20241201

20241202

PMC11605268

10.1002/art.42960

39054665