ECP as a potential treatment for liver rejection after transplantation – influence of cell death on T cell activation

Use of marginal livers in transplantation is increasing, leading to more complications resulting from pre-existing tissue damage and worse ischemia-reperfusion injury (IRI). Consequently, there is a major research focus on reducing early transplant injury and inflammation, which is partly driven by IL-17-secreting γδ T cells. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy applied in management of heart and lung transplant rejection. ECP leverages the potent suppressive effects of apoptotic cells, to control T cell-mediated diseases and to dampen acute and chronic inflammation.

In this study, we explored mechanisms of αβ and γδ T cell suppression by ECP using indirect coculture experiments. Apoptotic and pre-apoptotic PBMCs were obtained from clinical ECP products. These were indirectly cocultured with CD3/28/2-stimulated human T cells across a transwell membrane. The activation status of T cells was assessed by flow cytometry after 24h and 48h. Notably, we observed a reduction in CD69 expression in αβ (7.25±11.99%, p=0.0244) and γδ (9.26±19.62%, p=0.0302) T cells in ECP-treated cultures compared to control cultures (n=14).

Our preliminary results support the hypothesis that apoptotic cell-derived, transwell-permeating factors influence T cell activation. These factors may include soluble mediators (such as cytokines, metabolites or miRNAs) and extracellular vesicles. In the clinical setting, we might expect suppressive factors, especially as particulates, to accumulate in liver after intravenous infusion of ECP products. Hence, we speculate that factors release by apoptotic PBMC may be therapeutically useful in controlling pathological immune responses after liver transplantation through suppression of IL-17-secreting γδ T cells, amongst other subsets.

Publication History

Article published online:
20 January 2025