Adaptive NKG2C(+) NK Cell Response and the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C(+) NK cells. The distribution of NKG2C(+) NK cells and NKG2C genotypes (NKG2C(+/+), NKG2C(+/del), NKG2C(del/del)) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts. Assessment of CMV viremia was restricted to symptomatic cases in the retrospective study, but was regularly monitored in the prospective cohort. Overall, the proportions of NKG2C(+) NK cells were significantly higher in KTRs who had suffered posttransplant symptomatic CMV infection in the cross-sectional study. Yet, along the prospective follow-up (3, 6, 12, and 24 mo), posttransplant NKG2C(+) NK cell expansions were not observed in every patient with detectable viremia who received preemptive antiviral therapy, suggesting that the adaptive NK cell response may be inversely related with the degree of CMV control. Remarkably, the incidence of posttransplant viremia was reduced among cases with high pretransplant levels of NKG2C(+) NK cells. The NKG2C genotype distribution was comparable in KTR and healthy controls, and greater proportions of NKG2C(+) cells were detected in NKG2C(+/+) than in NKG2C(+/del) patients. Yet, a trend toward increased NKG2C(+/del) and reduced NKG2C(+/+) frequencies associated with symptomatic infection was appreciated in both cohorts. Altogether, our results indirectly support that adaptive NKG2C(+) NK cells are involved in the control of CMV in KTRs.