title: Immune responsiveness against allogeneic platelet transfusions is determined by the recipient's major histocompatibility complex class II phenotype.
abstract: BACKGROUND
  Immunoglobulin G (IgG) anti-platelet (PLT) immunity has been shown to be initiated by indirect allorecognition where recipient T cells recognize donor PLT antigens presented by class II molecules encoded by the major histocompatibility complex (MHC) on recipient antigen-presenting cells. To understand how the recipient's MHC class II molecules may influence PLT alloimmunity, immune responsiveness against transfused PLTs was tested in different mouse strains.
  
  
  METHODS
  Various inbred and mutant mouse strains were transfused with allogeneic PLTs and IgG donor antibodies were measured by flow cytometry.
  
  
  RESULTS
  When recipient mice, expressing both MHC class II I-A and MHC class II I-E molecules, were transfused weekly with allogeneic PLTs, high titers of IgG donor antibodies were generated. In comparison, however, recipient mice expressing only MHC class II I-A molecules had significantly (p < 0.001) reduced IgG antibody responsiveness against PLT transfusions. The low IgG responder status against allogeneic PLT transfusions was rescued in transgenic mice expressing I-E molecules and in mice genetically deficient in either beta2-microglobulin or CD8+ T cells.
  
  
  CONCLUSIONS
  IgG immune responsiveness against allogeneic PLT transfusions is dependent on recipient expression of I-E MHC class II molecules, whereas I-A expression is linked with CD8-mediated suppression of PLT immunity. The data suggest that strategies to modify recipient MHC class II presentation of donor PLT antigens would be effective in eliminating PLT alloimmunity.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Sayeh
authors.forename: Rukshana
authors.initials: R
authors.lastname: Aslam
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Speck
authors.forename: Hoang
authors.initials: H
authors.lastname: Le-Tien
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010641:Phenotype; D017713:Platelet Transfusion; D014184:Transplantation, Homologous / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency
chemical_list: D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007074:Immunoglobulin G; D001613:beta 2-Microglobulin