Pre-transplant infusion of donor leukocytes treated with extracorporeal photochemotherapy induces immune hypo-responsiveness and long-term allograft survival in murine models

Jennifer Schneiderman*, Longhui Qiu, Xin Yi Yeap, Xin Kang, Feibo Zheng, Junsheng Ye, Yan Xie, Jiao Jing Wang, Yuvaraj Sambandam, James Mathew, Lin Li, Joseph Leventhal, Richard L. Edelson, Zheng Jenny Zhang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant rejection by modulating the recipient’s own blood cells. We sought to induce donor-specific hypo-responsiveness of SOT recipients by infusing ECP-treated donor leukocytes prior to transplant. To this end, we utilized major histocompatibility complex mismatched rodent models of allogeneic cardiac, liver, and kidney transplantation to test this novel strategy. Leukocytes isolated from donor-matched spleens for ECP treatment (ECP-DL) were infused into transplant recipients seven days prior to SOT. Pre-transplant infusion of ECP-DL without additional IS was associated with prolonged graft survival in all models. This innovative approach promoted the production of tolerogenic dendritic cells and regulatory T-cells with subsequent inhibition of T-cell priming and differentiation, along with a significant reduction of donor-specific T-cells in the spleen and grafts of treated animals. This new application of donor-type ECP-treated leukocytes provides insight into the mechanisms behind ECP-induced immunoregulation and holds significant promise in the prevention of graft rejection and reduction in need of global immune suppressive therapy in patients following SOT.

Original languageEnglish (US)
Article number7298
JournalScientific reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General

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