Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

[摘要] Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of V δ 2neg γδ T cells in controlling CMV infection. Here, we assessed if V δ 2neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). V δ 2neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of V δ 2neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A V δ 2neg γδ 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, V δ 2neg γδ 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 delayed V δ 2neg γδ T cell expansion ( P <0.001). In conclusion, longitudinal surveillance of V δ 2neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.

[学科分类] 泌尿医学