title: Patients at high risk for CMV infection and disease show delayed CD8+ T-cell immune recovery after allogeneic stem cell transplantation.
abstract: Human cytomegalovirus (CMV) is a major cause of death after transplantation. The frequency of pp65-specific T cells was examined in 38 HLA-A2+ stem cell recipients during the first year after transplantation. Patients were divided into four groups based on donor/recipient serostatus: d+/r+ (n=17), d+/r- (n=7), d-/r+ (n=9) and d-/r- (n=5). Peripheral blood mononuclear cells were stimulated with the CMVpp65 peptide NLVPMVATV, and the specific T-cell frequency was assessed by interferon gamma (IFN-gamma) ELISPOT assay. Responding T cells were characterized by flow cytometry revealing a terminal differentiated effector phenotype. Surveillance of CMV infection was carried out by real-time polymerase chain reaction (n=26) or immunofluorescence (n=12). Infection was present in 7/9 d-/r+ high-risk patients, and CMV disease occurred exclusively in this group with delayed or absent virus-specific T-cell recovery. In contrast, 16/24 intermediate-risk patients showed CMV-specific T cells. Our data suggest that CMV infection and disease rates are elevated in high-risk patients with delayed CMV-specific T-cell immune reconstitution and lower in those with early recovery of T-cell immunity. We recommend preferring CMV seropositive donors for CMV seropositive recipients, as this should lead to durable CMV-specific T-cell responses soon after transplantation with consecutive protection from CMV disease.
authors.affiliation: Department of Internal Medicine III, Charité, Campus Benjamin Franklin, Hindenburgdamm, Berlin, Germany. susanne.ganepola@charite.de
authors.forename: S
authors.initials: S
authors.lastname: Ganepola
authors.forename: C
authors.initials: C
authors.lastname: Gentilini
authors.forename: U
authors.initials: U
authors.lastname: Hilbers
authors.forename: T
authors.initials: T
authors.lastname: Lange
authors.forename: K
authors.initials: K
authors.lastname: Rieger
authors.forename: J
authors.initials: J
authors.lastname: Hofmann
authors.forename: M
authors.initials: M
authors.lastname: Maier
authors.forename: U G
authors.initials: UG
authors.lastname: Liebert
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.forename: E
authors.initials: E
authors.lastname: Engelmann
authors.forename: R
authors.initials: R
authors.lastname: Heilbronn
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: L
authors.initials: L
authors.lastname: Uharek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D015789:HLA-A2 Antigen / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010455:Peptides / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D020127:Recovery of Function / Q000276:immunology*; D012307:Risk Factors; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D015789:HLA-A2 Antigen; D010455:Peptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma