# Suppressive CD8+ T‐Cells Are Key Cellular Mediators of Extracorporeal Photopheresis

## TL;DR

Extracorporeal photopheresis (ECP) works by boosting suppressive CD8+ T-cells, which may explain its immune-modulating effects in various diseases.

## Contribution

The study identifies suppressive CD8+ T-cells as a key mechanism of ECP's effects, offering a unifying explanation across different conditions.

## Key findings

- ECP protected mice from disease and reduced CNS pathology, relying on CD8+ T-cells.
- Patients undergoing ECP showed increased suppressive CD8+ T-cells within a month.
- Enhanced suppressive capacity of CD8+ T-cells was observed in ECP-treated patients.

## Abstract

Extracorporeal photopheresis (ECP) is a widely utilized immunomodulatory procedure with an incompletely defined mechanism. In graft‐versus‐host disease (GvHD) and transplant rejection, ECP is thought to induce immune tolerance by increasing regulatory CD4+ T‐cells, whereas in cutaneous T cell lymphoa it may enhance dendritic cell–mediated antigen presentation and cytotoxic T cell activity. We investigated the role of CD8+ T cells in ECP using a murine model of multiple sclerosis (MS). ECP protected mice from disease, mitigated CNS pathology, and was dependent on CD8+ T cells. Translation to patients revealed increased numbers of suppressive CD8+ T‐cells. Functional assays identified enhanced suppressive capacity of CD8+ T‐cells in ECP patients and longitudinal studies found this occurred within 1 month of starting ECP. Using both a murine model and clinical samples, our findings reveal a mechanistic role for suppressive CD8+ T‐cells in mediating the effects of ECP, potentially providing a unifying mechanism for ECP's apparently dichotomous effects.