title: Rapid reconstitution of CD4 T cells and NK cells protects against CMV-reactivation after allogeneic stem cell transplantation.
abstract: Epstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT).
  
  
  
  Here we investigated the role of immune cell reconstitution in the onset and subsequent severity of EBV- and CMV-reactivation. To this end, 116 patients were prospectively sampled for absolute T cell (CD4 and CD8), B-cell (CD19) and NK-cell (CD16 and CD56) numbers weekly post-SCT during the first 3 months and thereafter monthly until 6 months post-SCT. Viral load was monitored in parallel.
  
  
  
  In contrast to the general belief, we found that early T-cell reconstitution does not play a role in the onset of viral reactivation. CMV reactivation in the first 7 weeks after SCT however resulted in higher absolute CD8(+) T-cell numbers 6 months post-SCT in patients with high-level reactivation, many of which were CMV-specific. Interestingly, rapid reconstitution of CD4(+) T-cells, as well as NK cells and the presence of donor KIR3DL1, are associated with the absence of CMV-reactivation after SCT, suggestive of a protective role of these cells. In contrast, EBV-reactivations were not affected in any way by the level of immune reconstitution after SCT.
  
  
  
  In conclusion, these data suggest that CD4(+) T-cells and NK cells, rather than CD8(+) T-cells, are associated with protection against CMV-reactivation.
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.|Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Julia
authors.initials: J
authors.lastname: Drylewicz
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Ingrid M M
authors.initials: IM
authors.lastname: Schellens
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Gaiser
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Nening M
authors.initials: NM
authors.lastname: Nanlohy
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Esther D
authors.initials: ED
authors.lastname: Quakkelaar
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Henny
authors.initials: H
authors.lastname: Otten
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.|Department of Haematology, Utrecht, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Dorp
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Jacobi
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Ran
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Spijkers
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Dan
authors.initials: D
authors.lastname: Koning
authors.affiliation: Department of Virology, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Schuurman
authors.affiliation: Department of Haematology, VUMC, Amsterdam, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Meijer
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
authors.forename: Floortje L
authors.initials: FL
authors.lastname: Pietersma
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.|Department of Haematology, Utrecht, The Netherlands.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Kuball
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands. Debbie.van.baarle@rivm.nl.|Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. Debbie.van.baarle@rivm.nl.|Department of Immune Mechanisms, National Institute for Public Health and the environment (RIVM), Center for Infectious Disease Control, Antonie van leeuwenhoeklaan 9, Bilthoven, The Netherlands. Debbie.van.baarle@rivm.nl.
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D019610:Cytoprotection; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D054341:Receptors, KIR3DL1 / Q000378:metabolism; D012307:Risk Factors; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1
keywords: CMV; EBV; Immune reconstitution; Stem cell transplantation