title: Heterogeneous alterations in human alloimmunity associated with immunization.
abstract: BACKGROUND
  The presence of alloantibodies and/or alloreactive T cells in a patient prior to a transplant can impact graft outcome. Environmental factors, including therapeutic vaccinations, may influence the strength and/or specificity of alloimmunity.
  
  
  METHODS
  To address this issue, we prospectively evaluated the effects of two different immunization protocols in human subjects on cellular alloimmunity using an IFNgamma ELISPOT assay and on alloantibody reactivity by flow cytometric analysis of HLA-coated beads.
  
  
  RESULTS
  Vaccination/immunization was associated with augmentation of cellular and/or humoral alloimmune reactivity in >50% of the test subjects. The effects were heterogeneous in that some detected increases were transient, peaking 30-60 days postimmunization, whereas others persisted for the length of the study. Antibodies reactive to the immunizing agent did not cross react with the detected alloantibodies, suggesting that the augmentation of alloimmune reactivity was most likely due to a nonspecific adjuvant effect from the vaccine.
  
  
  CONCLUSIONS
  Therapeutic vaccinations can alter the strength of cellular and humoral alloimmunity in humans. The results suggest that serial immune monitoring of alloreactivity might be beneficial when immunizations are administered to potential transplant recipients.
authors.affiliation: Department of Immunology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Meagan
authors.initials: M
authors.lastname: Roddy
authors.forename: Michael
authors.initials: M
authors.lastname: Clemente
authors.forename: Emilio D
authors.initials: ED
authors.lastname: Poggio
authors.forename: Ronald
authors.initials: R
authors.lastname: Bukowski
authors.forename: Snehal
authors.initials: S
authors.lastname: Thakkar
authors.forename: Gunter
authors.initials: G
authors.lastname: Waxenecker
authors.forename: Hans
authors.initials: H
authors.lastname: Loibner
authors.forename: Gottfried
authors.initials: G
authors.lastname: Himmler
authors.forename: Donald E
authors.initials: DE
authors.lastname: Hricik
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D015551:Autoimmunity; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005770:Gastrointestinal Neoplasms / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000009:adverse effects*; D007518:Isoantibodies / Q000096:biosynthesis*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014611:Vaccination
chemical_list: D016207:Cytokines; D006680:HLA Antigens; D007518:Isoantibodies