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The following is a summary of “CD4⁺CD8α^low T cells in rheumatoid arthritis are clonally expanded and dependent on co-stimulation,” published in the July 2024 issue of Rheumatology by Beck et al.

CD4⁺CD8⁺ T cells, elevated in patients with rheumatoid arthritis (RA), are linked to joint erosions and appear even in pre-clinical RA stages.

Researchers conducted a retrospective study exploring the expansion of CD4⁺CD8⁺ T cells in patients with RA, focusing on T cell clonality and the response to targeted T cell therapies.

They utilized single-cell RNA and TCR sequencing data to evaluate co-receptor expression and T-cell receptor sequences, assessing the clonality of CD4⁺CD8⁺ T cells in patients with RA (n=3) and HCS (n=2). Flow cytometry measured peripheral CD4⁺CD8⁺ T cells and the subpopulations in RA (n=53), psoriatic arthritis (PsA) (n=52), and healthy donors (n=50). Additionally, CD4⁺CD8⁺T cell frequency changes were monitored prospectively in patients with RA undergoing abatacept therapy for 12 weeks.

The result showed an increase in CD4⁺ T cells expressing CD8α patients with RA compared to patients with PsA and HCs. Clonality analysis showed that the CD4⁺CD8α^low T cells are part of large T cell clones, which distinctly cluster from CD4⁺CD8^– T cell clones in the scRNA-seq gene expression analysis. Abatacept treatment significantly decreased the frequency of peripheral CD4⁺CD8α^low T cells, correlating with reduced disease activity.

Investigators concluded that in RA, clonal expansion of CD4⁺ T cell clones led to the development of peripheral CD4⁺CD8α^low T cells, which were linked to disease activity and reduced by abatacept treatment, potentially contributing to disease pathogenesis.

Source: acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/art.42960