Heterogeneous alterations in human alloimmunity associated with immunization

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 IFNγ 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.