title: Pro-tolerogenic effects of photodynamic therapy with TH9402 on dendritic cells.
abstract: A major goal in transplantation immunology is to develop strategies that can specifically promote tolerance to foreign cells and tissues without compromising other immune functions. Experimental induction of transplantation tolerance by dendritic cells (DCs) and/or T regulatory (Treg) cells can efficiently prevent graft-versus-host disease and organ graft rejection in animal models, and there is much hope that similar strategies in transplanted patients will provide an alternative to immunosuppression. Photodynamic therapy (PDT) is a therapeutic treatment for graft versus host disease and organ rejection that may operate via induction of tolerance. We investigated whether a new PDT therapy, based on exposure of cells to 4,5-dibromorhodamine methyl ester (TH9402), may operate via induction of tolerogenic DC. We developed an in vitro model to mimic the in vivo effect of re-infusing peripheral blood mononuclear cells (PBMCs) treated with PDT based on TH9402 (TH-PDT). TH-PDT-treated PBMCs were co-cultured with allogeneic immature monocyte-derived DCs. After 24 h, the phenotype and T-cell stimulatory capacity of the DCs was assessed. Following phagocytosis of TH-PDT PBMCs, DCs maintained an immature phenotype, produced significantly increased amounts of interleukin-10, and had a reduced allostimulatory capacity in comparison to mature DCs. In the context of transplantation, these data suggest that repeated exposure of circulating DCs to TH-PDT PBMCs may result in presentation of alloantigens under anti-inflammatory conditions and induction of antigen-specific tolerance.
authors.affiliation: Department of Medicine, University of British Columbia, and Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada. rbroady@interchange.ubc.ca
authors.forename: Raewyn
authors.initials: R
authors.lastname: Broady
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Megan K
authors.initials: MK
authors.lastname: Levings
mesh_terms: D003713:Dendritic Cells / Q000187:drug effects*; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D066298:In Vitro Techniques; D010778:Photochemotherapy; D012235:Rhodamines / Q000494:pharmacology*; D023001:Transplantation Tolerance / Q000187:drug effects*
chemical_list: D012235:Rhodamines; C121365:4,5-dibromorhodamine 123