Surveillance of gd T cells predicts cytomegalovirus infection resolution in kidney transplants

Abstract

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if aCMVmutant strainwith antiviral resistance emerges.MonitoringCMV-specific T cell response couldprovide relevant information for patient care.We and others have shown the involvement ofVd2neg gd Tcells in controllingCMVinfection. Here,we assessed ifVd2neggd T cell kinetics inperipheral bloodpredictCMVinfection resolution and emergence of a mutant strain in high-risk recipients of kidney transplants, incluDing 168 seronegative recipients receiving organs from seropositive donors (D+R2) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vd2neg gd T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vd2neg gd T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vd2neg gd T cell expansion rate of ?0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P,0.001). At 49 days of antiviral treatment, Vd2neg gd T cell expansion onset was associated with recovery,whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral-resistant mutant CMV strains was associated with delayedVd2neg gd T cell expansion (P,0.001). In conclusion, longitudinal surveillance ofVd2neg gd T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.