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

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• CD4+CD8+ T cells are elevated in rheumatoid arthritis (RA) and linked to joint damage.
• These cells are present in both early and established RA stages.
• Their role in RA pathogenesis and response to therapy requires further investigation.

Purpose of the Study:

• To investigate the expansion and clonality of CD4+CD8+ T cells in RA patients.
• To assess the impact of T cell-targeted therapy on these cells.

Main Methods:

• Utilized single-cell RNA and T cell receptor sequencing to analyze CD4+CD8+ T cell clonality in RA patients and controls.
• Quantified peripheral CD4+CD8+ T cell subpopulations in RA, psoriatic arthritis (PsA), and healthy donors via flow cytometry.
• Monitored changes in CD4+CD8+ T cell frequency during abatacept treatment in RA patients.

Main Results:

• RA patients exhibited increased CD4+ T cells expressing CD8α compared to PsA patients and healthy controls.
• CD4+CD8αlow T cells demonstrated clonal expansion and distinct gene expression patterns.
• Abatacept treatment led to a significant decrease in peripheral CD4+CD8αlow T cells, correlating with reduced disease activity.

Conclusions:

• Clonal expansion of CD4+ T cells in RA results in CD4+CD8αlow T cells associated with disease activity.
• These cells are reduced by abatacept treatment, suggesting a role in RA pathogenesis.
• Targeting CD4+ T cell expansion may be a therapeutic strategy for RA.