CMV-specific T-cell immunity, viral load, and clinical outcome in seropositive renal transplant recipients: a pilot study

Background: Cytomegalovirus (CMV) infection is still the leading opportunistic infection following solid organ transplantation. The aim of this prospective study of renal transplant recipients was to evaluate the dynamics of CMV-specific T-cells, viral load, and clinical symptoms of CMV infection. Methods: Levels of tetramer-selected CD8+ T-cells (TetraCD8), CMV-specific interferon-gamma producing CD8+ T-cells (IFN gamma CD8), and CD4+ T-cells (IFN gamma CD4), measured using major histocompatibility complex-tetramer and cytokine flow cytometry techniques, and CMV DNA were monitored monthly in 17 CMV-seropositive patients up to one yr (median 12 months, range 3-12) after transplantation and correlated to clinical outcome. Results: CMV DNAemia was detected in 94% of the patients, but only one patient developed CMV disease. CMV DNAemia > 1 million copies/mL was seen in asymptomatic patients. CMV-specific T-cells decreased rapidly after transplantation. TetraCD8 and IFN gamma CD8 regenerated within three months, whereas IFN gamma CD4 recovery was impaired up to one yr after transplantation. The proportion of IFN gamma CD4 at two months post-transplantation as compared with baseline, correlated strongly with the magnitude of the CMV DNAemia. Conclusions: Monitoring the reduction of IFN gamma CD4 compared with baseline during the first months after transplantation could be considered in predicting risk for high-grade CMV DNAemia and in deciding strategic approaches for pre-emptive and prophylactic therapy.