iScience. 2026 Jan 2;29(2):114612. doi: 10.1016/j.isci.2025.114612. eCollection 2026 Feb 20.
ABSTRACT
Insufficient healing of the Achilles tendon remains a frequent clinical challenge, creating a need for early markers that identify patients at risk of impaired healing. To examine whether adaptive immunity contributes to these outcomes, we analyzed T cell subsets in blood and hematoma collected during surgery. Patients with a higher CD4+/CD8+ T cell ratio at surgery reported more pain, showed reduced functional recovery, and greater tendon strain after 12 months. Conversely, elevated CD8+ T cell levels, and the CD28-/CD57+ memory subset, coincided with more favorable outcomes. We then investigated how these cells affect tendon healing by co-culturing human tenocytes with CD4+ or CD8+ T cells. Exposure to CD4+ T cells increased collagen type 3, IL-17 receptors and matrix metalloproteinases expression, indicating a shift toward impaired extracellular matrix organization. These results suggest that the CD4+/CD8+ T cell balance may serve as a prognostic marker and that modulating CD4+ T cell activity or IL-17 signaling could improve tendon repair.
PMID:41623480 | PMC:PMC12857407 | DOI:10.1016/j.isci.2025.114612