title: Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment.
abstract: BACKGROUND
  Donor white blood cells (WBCs) present in transfusion products can lead to immune sequelae such as production of HLA antibodies or graft-versus-host disease in susceptible transfusion recipients. Eliminating the immunogenicity of blood products may prove to be of clinical benefit, particularly in patients requiring multiple transfusions in whom allosensitization is common. This study examines a method of pathogen reduction based on ultraviolet light illumination in the presence of riboflavin. In addition to pathogens, WBCs treated with this system are affected and fail to stimulate proliferation of allogeneic peripheral blood mononuclear cells (PBMNCs) in vitro.
  
  
  METHODS
  This study sought to determine the mechanisms regulating this loss of immunogenicity. Treated cells were examined for surface expression of a number of molecules involved in activation and adhesion, viability, cell-cell conjugation, and ability to stimulate immune responses in allogeneic PBMNCs.
  
  
  RESULTS
  Compared with untreated controls, ultraviolet (UV)-irradiated antigen-presenting cells showed slightly reduced surface expression of HLA Class II and costimulatory molecules and had more significant reductions in surface expression of a number of adhesion molecules. Furthermore, treated cells had a severe defect in cell-cell conjugation. The observed loss of immunogenicity was nearly complete, with UV-irradiated cells stimulating barely measurable interferon-gamma production and no detectable STAT-3, STAT-5, or CD3-epsilon phosphorylation in allospecific primed T cells.
  
  
  CONCLUSIONS
  These results suggest that defective cell-cell adhesion prevents UV-irradiated cells from inducing T-cell activation.
authors.affiliation: Department of Laboratory Medicine and Medicine, Blood Systems Research Institute, University of California, San Francisco, California, USA. rjackman@bloodsystems.org
authors.forename: Rachael P
authors.initials: RP
authors.lastname: Jackman
authors.forename: John W
authors.initials: JW
authors.lastname: Heitman
authors.forename: Susanne
authors.initials: S
authors.lastname: Marschner
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Goodrich
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
mesh_terms: D001793:Blood Preservation / Q000379:methods*; D001803:Blood Transfusion; D017848:Blood-Borne Pathogens / Q000528:radiation effects; D015815:Cell Adhesion Molecules / Q000276:immunology; D016923:Cell Death / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000528:radiation effects; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D008213:Lymphocyte Activation; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012256:Riboflavin / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D015815:Cell Adhesion Molecules; D006680:HLA Antigens; D007519:Isoantigens; D017319:Photosensitizing Agents; D012256:Riboflavin
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