title: Role of cytomegalovirus (CMV)-specific polyfunctional CD8+ T-cells and antibodies neutralizing virus epithelial infection in the control of CMV infection in an allogeneic stem-cell transplantation setting.
abstract: The role of cytomegalovirus (CMV)-specific polyfunctional CD8+ T-cells and that of antibodies neutralizing virus epithelial infection (AbNEI) in the control of CMV DNAemia were investigated in 39 CMV-seropositive allogeneic stem-cell transplant (Allo-SCT) recipients with (n = 24) or without (n = 15) CMV DNAemia. AbNEI levels were monitored prospectively by means of a neutralization assay employing retinal epithelial cells (ARPE-19) and the recombinant CMV strain BADrUL131-Y4. Quantification of CMV-specific polyfunctional CD8+ T-cells (expressing two or three of the following markers: IFN-γγ, TNF-α and CD107a) in whole blood was performed by flow cytometry for intracellular cytokine staining. We found no differences in the dynamic pattern of AbNEI in patients with or without subsequent CMV DNAemia. Baseline and peak AbNEI titres were not predictive of the dynamics of CMV replication within episodes. No correlation was found between CMV DNA loads and AbNEI levels during episodes of CMV DNAemia (ρ = 0.09; 95 % confidence interval - 0.52 to 0.64; P = 0.78). The detection of pp65/IE-1 CMV-specific polyfunctional CD8+ T-cells was associated with low-level virus replication within subsequent episodes of CMV DNAemia. Interestingly, the presence of AbNEI titres (inverse) >4.7 log2 was predictive of the occurrence of CMV DNAemia (sensitivity, 83 %; specificity, 80 %). Our findings provide an insight to the role of humoral and cellular immunity in the control of CMV infection in an Allo-SCT setting.
authors.affiliation: Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Giménez
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Blanco-Lobo
authors.affiliation: Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Muñoz-Cobo
authors.affiliation: Hematology and Medical Oncology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
authors.affiliation: Hematology and Medical Oncology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Amat
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez-Romero
authors.affiliation: Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain.|Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Navarro
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000276:immunology; D000914:Antibodies, Viral / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D004848:Epithelium / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014184:Transplantation, Homologous / Q000009:adverse effects; D014766:Viremia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral