title: Inconsistent responses of cytomegalovirus-specific T cells to pp65 and IE-1 versus infected dendritic cells in organ transplant recipients.
abstract: CD4(+) and CD8(+) T cells specific for human cytomegalovirus (HCMV) and two immunodominant HCMV antigens (pp65 and IE-1) were monitored in 20 solid organ transplant recipients undergoing primary (n = 4) or reactivated (n = 16) HCMV infection during the first year after transplantation by using as a stimulator either HCMV-infected autologous dendritic cells (DCs) or pp65- or IE-1 peptide mixtures. Turnaround times for test performance were 7 days for infected DCs and 24 h for peptides. Using infected DCs, HCMV-specific T-cell restoration occurred in all patients for CD8(+) and in 18/20 (90%) for CD4(+) T-cell subpopulations, resulting in virus clearance from blood. Using peptide mixtures, T-cell responses were less frequently detected. In detail, 14 (70%) patients showed pp65-specific CD8(+) T cells and 10 (50%) patients IE-1-specific CD8(+) T cells, whereas pp65-specific CD4(+) T cells were detected in 14 (70%) patients, and IE-1-specific CD4(+) T cells in three (15%) patients only. Protection from HCMV infection was associated with the presence of a HCMV-specific T-cell response directed against multiple viral proteins, but not against pp65 or IE-1 only. In conclusion, the use of pp65 and IE-1 peptide mixtures for rapid monitoring of HCMV-specific T-cell responses in solid organ transplant recipients underestimates the actual T-cell immune response against HCMV.
authors.affiliation: Servizio di Virologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Lilleri
authors.forename: P
authors.initials: P
authors.lastname: Zelini
authors.forename: C
authors.initials: C
authors.lastname: Fornara
authors.forename: G
authors.initials: G
authors.lastname: Comolli
authors.forename: G
authors.initials: G
authors.lastname: Gerna
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology; D016377:Organ Transplantation; D010750:Phosphoproteins / Q000276:immunology*; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015534:Trans-Activators / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; C094775:IE-1 protein, murine cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa