title: Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection.
abstract: BACKGROUND
  Human cytomegalovirus infection is the most frequent viral complication in patients undergoing hematopoietic stem cell transplantation. We investigated the development of human cytomegalovirus-specific T cells in adult recipients of hematopoietic stem cell transplants.
  
  
  METHODS
  From May 2003 through October 2006 a total of 45 patients were monitored for human cytomegalovirus-specific T-cell reconstitution. Human cytomegalovirus-infected autologous dendritic cells were used as a stimulus to detect interferon-gamma-producing human cytomegalovirus-specific CD8(+) and CD4(+) T cells during the first year after transplantation. Interleukin-2 production by specific T cells was also determined.
  
  
  RESULTS
  Human cytomegalovirus infection was detected in the blood of 39/45 patients at a median of 29 days after transplantation. Human cytomegalovirus-specific T-cell reconstitution followed reactivation of latent human cytomegalovirus infection at a median time of about 2 months after transplantation. Only donor human cytomegalovirus-seronegativity and bone marrow as a stem cell source were found to delay specific T-cell reconstitution significantly. Levels of three CD8(+) and one CD4(+) human cytomegalovirus-specific T-cells/microL blood had a positive predictive value of around 80% for identifying patients able to control human cytomegalovirus infection spontaneously. Five patients who received high doses of steroids for treatment of graft-versus-host disease developed human cytomegalovirus infection requiring pre-emptive treatment despite high levels of interferon-gamma-producing T cells in response to human cytomegalovirus. Specific interleukin-2 production was not detected in patients with human cytomegalovirus infection requiring treatment, while 90% of patients who spontaneously controlled human cytomegalovirus infection had T cells that produced interleukin-2 and interferon-gamma.
  
  
  CONCLUSIONS
  Pre-transplant human cytomegalovirus infection of the recipient is a major factor driving human cytomegalovirus-specific immune reconstitution. Control of human cytomegalovirus infection likely requires the presence of both interferon-gamma and interleukin-2 producing T cells. Corticosteroid treatment may favor active viral replication even in patients with specific T cells.
authors.affiliation: Servizio di Virologia, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lilleri
authors.forename: Chiara
authors.initials: C
authors.lastname: Fornara
authors.forename: Antonella
authors.initials: A
authors.lastname: Chiesa
authors.forename: Daniela
authors.initials: D
authors.lastname: Caldera
authors.forename: Emilio Paolo
authors.initials: EP
authors.lastname: Alessandrino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gerna
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D020127:Recovery of Function / Q000276:immunology*; D013997:Time Factors; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: C050678:IE1 protein, Human herpesvirus 1; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma