Protective Cytomegalovirus (CMV)-Specific T-Cell Immunity Is Frequent in Kidney Transplant Patients without Serum Anti-CMV Antibodies.

The absence of anti-cytomegalovirus (CMV) immunoglobulin G (IgG) is used to classify pretransplant patients as naïve for CMV infection (CMV patients). This study assessed whether pretransplant CMV-specific T-cell immunity exists in CMV patients and whether it protects against CMV infection after kidney transplantation. The results show that CMV-specific CD137IFNγCD4 and CD137IFNγCD8 memory T cells were present in 46 and 39% of CMV patients ( = 28) although at much lower frequencies compared to CMV 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 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 patients (1 versus 45 ASC/10 cells in CMV patients). CMV patients with pretransplant CMV-specific CD137IFNγCD4 T cells had a lower risk to develop CMV viremia after transplantation with a CMV donor kidney (relative risk: 0.43,  = 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 donor.