title: Reconstitution of protective immune responses against cytomegalovirus and varicella zoster virus does not require disease development in pediatric recipients of umbilical cord blood transplantation.
abstract: CMV and varicella zoster virus (VZV) are significant causes of morbidity and mortality following umbilical cord blood transplantation (UCBT). However, the kinetics of reconstitution and protective potential of antiviral cell-mediated immune responses following UCBT remain poorly characterized. In this study, the reconstitution of CMV- and VZV-specific T cell responses was assessed using IFN-γ ELISPOT in 28 children who underwent UCBT to treat hematological or inherited disorders. Barely detectable in the first 3 mo posttransplantation, CMV- and VZV-specific T cell responses were observed in 30.4% and 40.3% of study subjects after 36 mo of follow-up. Four of five CMV-seropositive subjects developed detectable levels of circulating CMV DNA (DNAemia), and 5 of 17 VZV-seropositive patients experienced herpes zoster during the posttransplant period. Four CMV-seronegative subjects developed IFN-γ responses against CMV, and four subjects developed a VZV-specific IFN-γ response without clinical signs of infection. No CMV- or VZV-related events were observed in study subjects following the development of CMV- or VZV-specific responses > 150 spot-forming units/10(6) PBMCs, consistent with T cell-mediated protection. Finally, famciclovir prophylaxis did not strictly prevent the reconstitution of the VZV-specific T cell repertoire, because the frequency of T cells producing IFN-γ in response to VZV Ags reached levels consistent with protection in two nonzoster subjects. Monitoring of CMV- and VZV-specific cell-mediated immunity could inform immunocompetence and guide the initiation and cessation of antiherpetic prophylaxis in UCBT recipients.
authors.affiliation: Unité d'Immunopathologie Virale, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec H3T 1C5, Canada.
authors.forename: Natacha
authors.initials: N
authors.lastname: Merindol
authors.forename: Insaf
authors.initials: I
authors.lastname: Salem Fourati
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Brito
authors.forename: Anne-Julie
authors.initials: AJ
authors.lastname: Grenier
authors.forename: Emily
authors.initials: E
authors.lastname: Charrier
authors.forename: Paulo
authors.initials: P
authors.lastname: Cordeiro
authors.forename: Martine
authors.initials: M
authors.lastname: Caty
authors.forename: Samira
authors.initials: S
authors.lastname: Mezziani
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malette
authors.forename: Michel
authors.initials: M
authors.lastname: Duval
authors.forename: Carolina
authors.initials: C
authors.lastname: Alfieri
authors.forename: Philippe
authors.initials: P
authors.lastname: Ovetchkine
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Hugo
authors.initials: H
authors.lastname: Soudeyns
mesh_terms: D000293:Adolescent; D000328:Adult; D002644:Chickenpox / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D030342:Genetic Diseases, Inborn / Q000276:immunology / Q000628:therapy; D006402:Hematologic Diseases / Q000276:immunology / Q000628:therapy; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D020127:Recovery of Function / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D007371:Interferon-gamma