Expanded senescent CD8 T cells in IMID patients are associated with distinct inflammatory cytokines

Area of Science:

• Immunology
• Gerontology
• Rheumatology

Background:

• Immune aging, characterized by senescent T cells, is increasingly recognized in chronic diseases.
• The role of T cell senescence in immune-mediated inflammatory diseases (IMIDs) remains incompletely understood.

Purpose of the Study:

• To investigate the proportion of senescent T cells (T4sen and T8sen) in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA).
• To assess the impact of anti-TNF therapy on T cell senescence.
• To explore associations between T cell senescence, cytokines, and disease characteristics.

Main Methods:

• Flow cytometry was used to quantify circulating T4sen and T8sen proportions in RA, SpA, Sjögren's syndrome (SjD), healthy donors, and cancer patients.
• Cytokine levels (IL-6, IP-10) were measured at baseline.
• Patients were assessed at baseline and 3 months after initiating anti-TNF treatment.

Main Results:

• T8sen, but not T4sen, were significantly accumulated in IMID patients compared to healthy donors and cancer patients.
• CMV-seropositivity was linked to increased T8sen accumulation.
• T8sen levels correlated with IL-6 in SpA and IP-10 in SjD patients.
• Anti-TNF treatment did not alter T8sen proportions in RA and SpA patients, with a trend towards increase in non-responders.

Conclusions:

• Senescent CD8 T cells are enriched in IMID patients, indicating immune aging is a shared feature of these chronic inflammatory conditions.
• The association of T8sen with specific inflammatory cytokines suggests a role in shaping immune responses within IMIDs.