# CD137 Signaling Modulates Vein Graft Atherosclerosis by Driving T-Cell Activation and Regulating Intraplaque Angiogenesis

## TL;DR

This study shows that CD137 signaling influences vein graft atherosclerosis by activating T-cells and controlling blood vessel growth in plaques.

## Contribution

The study reveals CD137 as a novel target for early immunomodulation to reduce vein graft failure.

## Key findings

- CD8+ T-cells accumulate in atherosclerotic vein grafts and are rapidly activated after surgery.
- CD137 signaling promotes T-cell activation and IFN-γ expression, mainly in CD8+ cells.
- Early CD137 agonism reduces plaque growth and angiogenesis, while its silencing worsens atherosclerosis.

## Abstract

•CD8+, and to a lesser extent CD4+, T-cells accumulated over time in murine unstable, atherosclerotic vein graft lesions, while their activation occurs rapidly after surgery.•CD137 signaling regulated predominantly CD8+ T-cell activation, effector-memory differentiation, and IFN-γ expression.•Early immunomodulation (1 day after surgery) through agonistic CD137 treatment improved vein graft remodeling and diminished intraplaque angiogenesis, whereas silencing of CD137 signaling by antagonistic antibodies aggravated atherosclerotic lesion development.

CD8+, and to a lesser extent CD4+, T-cells accumulated over time in murine unstable, atherosclerotic vein graft lesions, while their activation occurs rapidly after surgery.

CD137 signaling regulated predominantly CD8+ T-cell activation, effector-memory differentiation, and IFN-γ expression.

Early immunomodulation (1 day after surgery) through agonistic CD137 treatment improved vein graft remodeling and diminished intraplaque angiogenesis, whereas silencing of CD137 signaling by antagonistic antibodies aggravated atherosclerotic lesion development.

Atherosclerotic vein graft failure still presents a major problem. T-cells have been identified as one of the most abundant immune cell subset in atherosclerotic plaques. Their role, however, remains only partly understood. Using a murine vein graft model for advanced, unstable atherosclerotic lesions, we find that T-cells accumulate over time in atherosclerotic vein grafts, and appear to be activated rapidly after engraftment, demonstrated by increased expression of CD137 on plaque T-cells. Targeting of CD137 affects intraplaque angiogenesis and plaque growth, which renders CD137 a promising target for early immunomodulation to reduce atherosclerotic vein graft failure.