Senescent CD8+ T Cells Linked to Pathogenesis in Spondyloarthritis and Psoriatic Arthritis

A recent study published in Arthritis & Rheumatology highlights the role of terminally differentiated CD8+ T cells in the pathogenesis of radiographic axial spondyloarthritis (r-axSpA) and psoriatic arthritis (PsA). Researchers identified a senescent CD8+ T cell subset with enhanced invasive potential, cytotoxicity, and proinflammatory activity in patients with SpA, distinguishing it from patients with rheumatoid arthritis and healthy donors. 

Peripheral blood analysis of 128 patients with r-axSpA and 60 PsA revealed an increased population of CD8+ T cells with spontaneous migratory capability, even in the absence of chemokine stimulation. These cells, enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) phenotypes, expressed high levels of cytolytic molecules, including granzyme B, perforin, and granulysin, along with the proinflammatory cytokine TNFα. 

Transcriptome analysis confirmed a cytolytic and natural killer-like gene expression profile in these cells. Additionally, researchers observed DNA damage response activation, telomere shortening, and dysfunction in this subset, implicating cellular senescence as a contributor to their behavior. 

These findings suggest that this unique subset of CD8+ T cells may drive inflammation and tissue damage in SpA. "This subset represents a possible player in disease pathogenesis," the authors stated, emphasizing its potential as a biomarker or therapeutic target. 

The spontaneous migratory behavior and cytotoxicity of these cells underscore their capacity to infiltrate target tissues and amplify inflammatory cascades, potentially linking them to disease severity and progression in SpA. 

This study identifies a senescent, cytotoxic CD8+ T cell population with intrinsic invasive potential as a key feature in SpA pathogenesis. Targeting these cells could open new avenues for understanding disease mechanisms and developing therapies for spondyloarthritis. Further research is needed to explore their role across disease stages and subtypes. 

Reference
Paldino G, Tedeschi V, Proganò V, et al. An immunosenescent CD8+ T cell subset in patients with axial spondyloarthritis and psoriatic arthritis links spontaneous motility to telomere shortening and dysfunction. Arthritis Rheumatol. Published January 21, 2025. doi:10.1002/art.43109