title: Early reconstitution of effector memory CD4+ CMV-specific T cells protects against CMV reactivation following allogeneic SCT.
abstract: Reactivation of CMV is a common complication following allogeneic haematopoietic SCT and is associated with significant morbidity and mortality. The relative importance of the CD4+ and CD8+ components of the CMV-specific immune response in protection from reactivation is unclear. The CMV-specific CD4+ and CD8+ immune response was measured at serial time points in 32 patients following allogeneic HSCT. Intracellular cytokine staining following CMV lysate stimulation and HLA-peptide tetramers were used to determine CMV-specific CD4+ and CD8+ responses, respectively. A deficient CMV-specific CD4+ T-cell immune response within the first 30-50 days post transplant was associated with high risk of viral reactivation. Patients with combined impairment of the CD4+ and CD8+ immune response within the first 100 days were susceptible to late viral reactivation. The frequency of CMV-specific CD4+ T cells correlated with CMV-specific CD8+ T cells, comprising 10% of the whole T-cell repertoire. Early CMV-specific CD4+ T-cell reconstitution was dominated by effector memory cells with normal levels of IL-2 resuming 6 months following transplantation. In summary, both CD4 and CD8 CMV-specific immune reconstitution is required for protection from recurrent activation. Measurement of the magnitude of the CMV-specific CD4+ immune response is useful in managing viral reactivation following HSCT.
authors.affiliation: CRUK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: B
authors.initials: B
authors.lastname: Pourgheysari
authors.forename: K P
authors.initials: KP
authors.lastname: Piper
authors.forename: A
authors.initials: A
authors.lastname: McLarnon
authors.forename: J
authors.initials: J
authors.lastname: Arrazi
authors.forename: R
authors.initials: R
authors.lastname: Bruton
authors.forename: F
authors.initials: F
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Cook
authors.forename: P
authors.initials: P
authors.lastname: Mahendra
authors.forename: C
authors.initials: C
authors.lastname: Craddock
authors.forename: P A H
authors.initials: PA
authors.lastname: Moss
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal