Mirasol PRT treatment of donor white blood cells prevents the development of xenogeneic graft‐versus‐host disease in Rag2–/–γc–/– double knockout mice

Abstract

Mirasol PRT (Navigant Biotechnologies) treatment utilizes exposure to light in the presence of riboflavin to introduce irreparable lesions to nucleic acids thereby inhibiting pathogen and WBC replication. The ability of Mirasol PRT-treated mononuclear cells (MNCs) to generate xenogeneic graft-versus-host disease (GVHD) responses was used to model transfusion-associated GVHD (TAGVHD). Pairs of human MNCs from five different individual donors that had or had not received Mirasol PRT treatment and contained 30 x 10(6) CD3+ cells were injected intraperitoneally into sublethally irradiated (350 cGy) Rag2(-/-)gamma c(-/-) double-knockout mice. Recipient mice were weighed and observed regularly and euthanized when they exhibited symptoms of GVHD or at termination of the experiment. Recipient lymphoid compartments were collected and phenotyped for the presence of human lymphoid cells. The presence of human cytokines and/or immunoglobulins in the recipient plasma was also used to detect the presence of human cells. Twelve of 14 mice injected with untreated cells developed xenogeneic GVHD, whereas 0 of 14 mice injected with Mirasol PRT-treated cells developed xenogeneic GVHD. End-stage xenogeneic GVHD in the recipients of untreated cells was characterized by the presence of splenic human cytolytic CD4+ and CD8+ cells, with high levels of interferon-gamma, interleukin-10, and xenoreactive antibodies in the plasma. Mirasol PRT treatment of the donor MNCs abolished xenogeneic GVHD responses, indicating that the use of Mirasol PRT treatment of blood products should prevent the development of TAGVHD.