title: BK polyomavirus-specific cellular immune responses are age-dependent and strongly correlate with phases of virus replication.
abstract: BK polyomavirus (BKPyV) infection is widespread and typically asymptomatic during childhood, but may cause nephropathy in kidney transplant recipients. However, there is only limited knowledge on BKPyV-specific immunity in children and adults, and its role in BKPyV-replication and disease posttransplant. We therefore characterized BKPyV-specific immunity from 122 immunocompetent individuals (1-84 years), 38 adult kidney recipients with (n = 14) and without BKPyV-associated complications (n = 24), and 25 hemodialysis (HD) patients. Blood samples were stimulated with overlapping peptides of BKPyV large-T antigen and VP1 followed by flow-cytometric analysis of activated CD4 T cells expressing interferon-γ, IL-2 and tumor necrosis factor-α. Antibody-levels were determined using enzyme-linked immunosorbent assay. Both BKPyV-IgG levels and BKPyV-specific CD4 T cell frequencies were age-dependent (p = 0.0059) with maximum levels between 20 and 30 years (0.042%, interquartile range 0.05%). Transplant recipients showed a significantly higher BKPyV-specific T cell prevalence (57.9%) compared to age-matched controls (21.7%) or HD patients (28%, p = 0.017). Clinically relevant BKPyV-replication was associated with elevated frequencies of BKPyV-specific T cells (p = 0.0002), but decreased percentage of cells expressing multiple cytokines (p = 0.009). In conclusion, BKPyV-specific cellular immunity reflects phases of active BKPyV-replication either after primary infection in childhood or during reactivation after transplantation. Combined analysis of BKPyV-specific T cell functionality and viral loads may improve individual risk assessment.
authors.affiliation: Department of Transplant and Infection Immunology, Institute of Virology, Saarland University, Homburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schmidt
authors.forename: C
authors.initials: C
authors.lastname: Adam
authors.forename: H H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: M W W
authors.initials: MW
authors.lastname: Janssen
authors.forename: M
authors.initials: M
authors.lastname: Wolf
authors.forename: J
authors.initials: J
authors.lastname: Dirks
authors.forename: P
authors.initials: P
authors.lastname: Kardas
authors.forename: T
authors.initials: T
authors.lastname: Ahlenstiel-Grunow
authors.forename: L
authors.initials: L
authors.lastname: Pape
authors.forename: T
authors.initials: T
authors.lastname: Rohrer
authors.forename: D
authors.initials: D
authors.lastname: Fliser
authors.forename: M
authors.initials: M
authors.lastname: Sester
authors.forename: U
authors.initials: U
authors.lastname: Sester
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001739:BK Virus / Q000276:immunology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D014779:Virus Replication; D055815:Young Adult
keywords: BKPyV; CD4 T cell; IFNγ; T cell; cytokine profiling; flow-cytometry; interferon-γ