title: Human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T cells are both required for prevention of HCMV disease in seropositive solid-organ transplant recipients.
abstract: In solid-organ transplant recipients (SOTR) the protective role of human cytomegalovirus (HCMV)-specific CD4+, CD8+ and γδ T-cells vs. HCMV reactivation requires better definition. The aim of this study was to investigate the relevant role of HCMV-specific CD4+, CD8+ and γδ T-cells in different clinical presentations during the post-transplant period. Thirty-nine SOTR underwent virologic and immunologic follow-up for about 1 year after transplantation. Viral load was determined by real-time PCR, while immunologic monitoring was performed by measuring HCMV-specific CD4+ and CD8+ T cells (following stimulation with autologous HCMV-infected dendritic cells) and γδ T-cells by flow cytometry. Seven patients had no infection and 14 had a controlled infection, while both groups maintained CD4+ T-cell numbers above the established cut-off (0.4 cell/µL blood). Of the remaining patients, 9 controlled the infection temporarily in the presence of HCMV-specific CD8+ only, until CD4+ T-cell appearance; while 9 had to be treated preemptively due to a viral load greater than the established cut-off (3×10(5) DNA copies/mL blood) in the absence of specific CD4+ T-cells. Polyfunctional CD8+ T-cells as well as Vδ2- γδ T-cells were not associated with control of infection. In conclusion, in the absence of HCMV-specific CD4+ T-cells, no long-term protection is conferred to SOTR by either HCMV-specific CD8+ T-cells alone or Vδ2- γδ T-cell expansion.
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gabanti
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bruno
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lilleri
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fornara
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zelini
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cane
authors.affiliation: Divisione di Nefrologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Migotto
authors.affiliation: Divisione di Cardiochirurgia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Sarchi
authors.affiliation: S. S. Virologia Molecolare, S. C. Microbiologia e Virologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Furione
authors.affiliation: Laboratori Sperimentali di Ricerca, Area Trapiantologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gerna
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D066027:Transplant Recipients; D019562:Viral Load