title: Differential effect of pretransplant blood transfusions on immune effector and regulatory compartments in HLA-sensitized and nonsensitized recipients.
abstract: BACKGROUND
  Blood transfusion (BT) may elicit both harmful and beneficial immune responses against a subsequent organ graft. Immune parameters of a single, non leukocyte-depleted BT were investigated in two groups: non-human leukocyte antigen (HLA)-sensitized recipients with a one-HLA-DR matched donor (protocolled BT [PBT]) and females with previous exposure to HLA alloantigens through pregnancy (donor-specific transfusion [DST]).
  
  
  METHODS
  Thirty-five percent of DST recipients and 9.5% of PBT recipients developed HLA antibodies after BT.Phenotypic and functional analyses were performed in pre-BT, 2 weeks post-BT, and more than 10 weeks post-BT samples (PBT: n=10; DST: n=14).
  
  
  RESULTS
  The number of donor-reactive interferon-γ-producing memory T cells increased 2 weeks post-BT, but only in the DST group, increased frequencies persisted beyond 10 weeks (P0.004). In the DST recipients, the proportion of natural killer cells (CD3(-)CD56(+)) significantly increased after BT (P=0.01), whereas in PBT recipients, the proportion of regulatoryT cells (CD4(+)CD25(+)Foxp3(+)CD127 low) significantly increased at 2 weeks post-BT (P=0.039). Microarray analysis confirmed increased activity of genes involved in function of natural killer cells,Tcells, and Bcells in DSTrecipients and increased expression of immune regulatory genes (galectin-1, Foxo3a, and follistatin-like 3) in PBT recipients. Galectin-1 expression by quantitative polymerase chain reaction was significantly enhanced in peripheral blood cells after PBT (P0.05).
  
  
  CONCLUSIONS
  Decreased immune effector mechanisms combined with an increased immune regulatory cell signature after HLA-DR-matched BT in nonsensitized patients is in line with clinical observations of improved outcome of a subsequent graft. Previous sensitization, however, may lead to HLA antibody formation and prolonged donor-specific memory T-cell reactivity after BT.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden UniversityMedical Center, Leiden, The Netherlands. m.eikmans@lumc.nl
authors.forename: Michael
authors.initials: M
authors.lastname: Eikmans
authors.forename: Marloes M
authors.initials: MM
authors.lastname: Waanders
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Paula P M C
authors.initials: PP
authors.lastname: van Miert
authors.forename: Jacqy D H
authors.initials: JD
authors.lastname: Anholts
authors.forename: Hans W
authors.initials: HW
authors.lastname: de Fijter
authors.forename: Anneke
authors.initials: A
authors.lastname: Brand
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D001803:Blood Transfusion; D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D009426:Netherlands; D020411:Oligonucleotide Array Sequence Analysis; D016035:Pancreas Transplantation / Q000276:immunology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D023001:Transplantation Tolerance / Q000235:genetics
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006680:HLA Antigens; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D007518:Isoantibodies; C522918:NCAM1 protein, human; D007371:Interferon-gamma