# CD4+ to CD8+ T cell imbalance drives poor Achilles tendon repair in patients

## TL;DR

A higher CD4+ to CD8+ T cell ratio in patients during surgery is linked to worse Achilles tendon healing and could help identify those at risk.

## Contribution

The study identifies a novel T cell ratio as a potential prognostic marker for Achilles tendon repair outcomes.

## Key findings

- Higher CD4+/CD8+ T cell ratio correlates with increased pain and worse functional recovery after 12 months.
- CD8+ memory T cells are associated with reduced tendon elongation and better healing outcomes.
- CD4+ T cells promote catabolic responses in tenocytes, affecting extracellular matrix organization.

## 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.

•CD4+/CD8+ T cell ratio at surgery predicts Achilles tendon healing outcome•CD8+ memory T cell subsets associate with reduced tendon elongation•CD4+ T cells drive IL-17-related catabolic responses in human tenocytes•T cell profiling enables early identification of patients at risk for poor repair

CD4+/CD8+ T cell ratio at surgery predicts Achilles tendon healing outcome

CD8+ memory T cell subsets associate with reduced tendon elongation

CD4+ T cells drive IL-17-related catabolic responses in human tenocytes

T cell profiling enables early identification of patients at risk for poor repair

Immunology; Cell biology