title: Prospective analysis of human cytomegalovirus DNAemia and specific CD8+ T cell responses in lung transplant recipients.
abstract: In lung transplant recipients (LuTRs), human cytomegalovirus (HCMV) DNAemia may be associated with HCMV disease and reduced survival of the allograft. Because T cells are essential for controlling HCMV replication, we investigated in this prospective study whether the kinetics of plasma HCMV DNA loads in LuTRs are associated with HCMV-specific CD8+ T cell responses, which were longitudinally assessed using a standardized assay. Sixty-seven LuTRs were monitored during the first year posttransplantation, with a mean of 17 HCMV DNA PCR quantifications and 11.5 CD8+ T cell tests performed per patient. HCMV-specific CD8+ T cell responses displayed variable kinetics in different patients, differed significantly before the onset of HCMV DNAemia in LuTRs who subsequently experienced episodes of DNAemia with high (>1000 copies/mL) and low plasma DNA levels (p = 0.0046, Fisher's exact test), and were absent before HCMV disease. In HCMV-seropositive LuTRs, high-level DNAemia requiring preemptive therapy occurred more frequently when HCMV-specific CD8+ T cell responses fluctuated, were detected only after HCMV DNA detection, or remained undetectable (p = 0.0392, Fisher's exact test). Thus, our data indicate that HCMV-specific CD8+ T cells influence the magnitude of HCMV DNAemia episodes, and we propose that a standardized measurement of CD8+ T cell immunity might contribute to monitoring the immune status of LuTRs posttransplantation.
authors.affiliation: Department of Virology, Medical University of Vienna, Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Weseslindtner
authors.forename: H
authors.initials: H
authors.lastname: Kerschner
authors.forename: D
authors.initials: D
authors.lastname: Steinacher
authors.forename: R
authors.initials: R
authors.lastname: Nachbagauer
authors.forename: M
authors.initials: M
authors.lastname: Kundi
authors.forename: P
authors.initials: P
authors.lastname: Jaksch
authors.forename: B
authors.initials: B
authors.lastname: Simon
authors.forename: L
authors.initials: L
authors.lastname: Hatos-Agyi
authors.forename: A
authors.initials: A
authors.lastname: Scheed
authors.forename: W
authors.initials: W
authors.lastname: Klepetko
authors.forename: E
authors.initials: E
authors.lastname: Puchhammer-Stöckl
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics*; D004279:DNA, Viral / Q000097:blood*; D006801:Humans; D016040:Lung Transplantation; D016133:Polymerase Chain Reaction; D011446:Prospective Studies
chemical_list: D004279:DNA, Viral