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 naive for CMV infection (CMVneg patients). This study assessed whether pretransplant CMV-specific T-cell immunity exists in CMVneg patients and whether it protects against CMV infection after kidney transplantation. The results show that CMV-specific CD137(+)IFN gamma(+)CD4(+) and CD137(+)IFN gamma(+)CD8(+) memory T cells were present in 46 and 39% of CMVneg patients (n = 28) although at much lower frequencies compared to CMVpos 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 CMVneg 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 CMVneg patients (1 versus 45 ASC/10(5) cells in CMVpos patients). CMVneg patients with pretransplant CMV-specific CD137(+)IFN gamma(+)CD4(+) T cells had a lower risk to develop CMV viremia after transplantation with a CMVpos 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 CMVpos donor.