title: Surveillance of γδ 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 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 Vδ2(neg) γδ T cells in controlling CMV infection. Here, we assessed if Vδ2(neg) 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). Vδ2(neg) γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2(neg) 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 Vδ2(neg) 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, Vδ2(neg) 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 Vδ2(neg) γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2(neg) γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.
authors.affiliation: Department of Nephrology, Transplantation, and Dialysis and.
authors.forename: Hannah
authors.initials: H
authors.lastname: Kaminski
authors.affiliation: Virology and National Center of Scientific Research(CNRS), Research Unit 5234, Bordeaux, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Garrigue
authors.affiliation: Department of Nephrology, Transplantation, and Dialysis and National Center of Scientific Research, Mix Unit of Research 5164, Bordeaux, France;
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.affiliation: Department of Nephrology, Transplantation, and Dialysis and.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Taton
authors.affiliation: Department of Nephrology, Transplantation, and Dialysis and National Center of Scientific Research, Mix Unit of Research 5164, Bordeaux, France;
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelet
authors.affiliation: National Center of Scientific Research, Mix Unit of Research 5164, Bordeaux, France; Immunology laboratories, Bordeaux University Hospital, Bordeaux, France;
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.affiliation: National Center of Scientific Research, Mix Unit of Research 5164, Bordeaux, France;
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
authors.affiliation: French Institute of Health and Medical Research (INSERM), Institute of Public Health and Epidemiology and Development (ISPED), Center U897-Epidemiology-Biostatistics, Bordeaux, France; and National Institute for Research in Computer Science and Control (INRIA), Statistics In Systems biology and Translational Medicine (SISTM) Team, Bordeaux, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.affiliation: Department of Nephrology, Transplantation, and Dialysis and National Center of Scientific Research, Mix Unit of Research 5164, Bordeaux, France; pierre.merville@chu-bordeaux.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D011379:Prognosis; D012074:Remission Induction; D013601:T-Lymphocytes
chemical_list: D000998:Antiviral Agents
keywords: cytomegalovirus; immunology; immunosuppression; kidney transplantation