Suppressive <scp>CD8</scp> + T‐Cells Are Key Cellular Mediators of Extracorporeal Photopheresis

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.