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In solid-organ transplant recipients (SOTR) the protective role of human cytomegalovirus (HCMV)-specific CD4 + , CD8 +  and γδ T-cells vs. HCMV reactivation requires better definition. The aim of this study was to investigate the relevant role of HCMV-specific CD4 + , CD8 +  and γδ T-cells in different clinical presentations during the post-transplant period. Thirty-nine SOTR underwent virologic and immunologic follow-up for about 1 year after transplantation. Viral load was determined by real-time PCR, while immunologic monitoring was performed by measuring HCMV-specific CD4 +  and CD8 +  T cells (following stimulation with autologous HCMV-infected dendritic cells) and γδ T-cells by flow cytometry. Seven patients had no infection and 14 had a controlled infection, while both groups maintained CD4 +  T-cell numbers above the established cut-off (0.4 cell/µL blood). Of the remaining patients, 9 controlled the infection temporarily in the presence of HCMV-specific CD8 +  only, until CD4 +  T-cell appearance; while 9 had to be treated preemptively due to a viral load greater than the established cut-off (3×10 5  DNA copies/mL blood) in the absence of specific CD4 +  T-cells. Polyfunctional CD8 +  T-cells as well as Vδ2 −  γδ T-cells were not associated with control of infection. In conclusion, in the absence of HCMV-specific CD4 +  T-cells, no long-term protection is conferred to SOTR by either HCMV-specific CD8 +  T-cells alone or Vδ2 −  γδ T-cell expansion.

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Human Cytomegalovirus (HCMV)-Specific CD4+ and CD8+ T Cells Are Both Required for Prevention of HCMV Disease in Seropositive Solid-Organ Transplant Recipients