The absence of anti-cytomegalovirus (CMV) immunoglobulin G (IgG) is used to classify pretransplant patients as naïve for CMV infection (CMV^neg patients). This study assessed whether pretransplant CMV-specific T-cell immunity exists in CMV^neg patients and whether it protects against CMV infection after kidney transplantation. The results show that CMV-specific CD137⁺IFNγ⁺CD4⁺ and CD137⁺IFNγ⁺CD8⁺ memory T cells were present in 46 and 39% of CMV^neg patients (n = 28) although at much lower frequencies compared to CMV^pos patients (median 0.01 versus 0.58% for CD4⁺ and 0.05 versus 0.64% for CD8⁺ T cells) with a less differentiated CD28-expressing phenotype. In line with these data, CMV-specific proliferative CD4⁺ and CD8⁺ T cells were observed in CMV^neg patients, which significantly correlated with the frequency of CMV-specific T cells. CMV-specific IgG antibody-secreting cells (ASC) could be detected at low frequency in 36% of CMV^neg patients (1 versus 45 ASC/10⁵ cells in CMV^pos patients). CMV^neg patients with pretransplant CMV-specific CD137⁺IFNγ⁺CD4⁺ T cells had a lower risk to develop CMV viremia after transplantation with a CMV^pos donor kidney (relative risk: 0.43, P = 0.03). In conclusion, a solitary CMV-specific T-cell response without detectable anti-CMV antibodies is frequent and clinically relevant as it is associated with protection to CMV infection following transplantation with a kidney from a CMV^pos donor.

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