A quantitative assay for Epstein-Barr virus-specific immunity shows interferon-γ producing CD8+T cells increase during immunosuppression reduction to treat posttransplant lymphoproliferative disease

Reduction of immunosuppression (RIS) to allow development or recovery of Epstein-Barr virus (EBV) immunity can be used to treat EBV-associated posttransplant lymphoproliferative disease (PTLD). Quantification of EBV-specific immunity would help assessment of the efficacy of RIS therapy. Use of intracellular cytokine staining and analysis by flow cytometry to monitor functional EBV-specific T-cell immunity was evaluated in healthy volunteers. The technique was then used to monitor EBV immunity in nine renal transplant patients with PTLD during RIS. The number of interferon (IFN)-gamma producing CD8+ T cells specific for EBV increased distinctly before regression of EBV+ PTLD tumors occurred. The findings confirm the importance of IFN-gamma producing CD8 + T cells in controlling the malignant EBV-transformed B cells of PTLD. The assay effectively quantified EBV immunity during RIS in transplant patients with PTLD.