title: Comprehensive phenotyping of regulatory T cells after liver transplantation.
abstract: Regulatory T cells (Tregs) play an important role in controlling alloreactivity after solid organ transplantation, but they may also impair antiviral immunity. We hypothesized that the Treg frequency and the Treg phenotype are altered in hepatitis C virus (HCV)-infected recipients of liver transplantation (LT) with possible prognostic implications. Tregs from 141 individuals, including healthy individuals, LT recipients with or without persistent HCV infections, and nontransplant patients with chronic HCV, were studied. A comprehensive phenotypic analysis was performed with multicolor flow cytometry, which included standard Treg markers [CD4(+), CD25(hi), CD127(-), and FoxP3(+) in addition to HLA DR, CCR7, CD45RA, CD62L, CD49d, CD39, ICOS and LAP-TGFβ stainings. Healthy individuals and LT patients displayed similar Treg frequencies and largely comparable Treg phenotypes, which were stable over time after transplantation. In contrast, Tregs with a CD45RA(-) CCR7(-) effector phenotype were enriched in LT recipients with chronic HCV versus HCV-negative transplant patients. HCV infection, rather than LT, altered the expression of functional markers on Tregs. A principal component analysis revealed distinct Treg phenotypes in HCV-infected LT recipients with rejection and patients with recurrent graft HCV. In conclusion, Treg phenotypes are altered in HCV-infected LT patients. An investigation of Tregs may possibly help to distinguish recurrent HCV from graft rejection. Further functional studies are needed to define the role of Tregs in determining the balance between antiviral and allogenic immunity.
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hanover, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Gronert Álvarez
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Fytili
authors.forename: Pothakamuri V
authors.initials: PV
authors.lastname: Suneetha
authors.forename: Anke R M
authors.initials: AR
authors.lastname: Kraft
authors.forename: Christin
authors.initials: C
authors.lastname: Brauner
authors.forename: Jerome
authors.initials: J
authors.lastname: Schlue
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
authors.forename: Christoph
authors.initials: C
authors.lastname: Meyer-Heithuis
authors.forename: Elmar
authors.initials: E
authors.lastname: Jaeckel
authors.forename: Juergen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D017093:Liver Failure / Q000175:diagnosis / Q000276:immunology / Q000601:surgery* / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D025341:Principal Component Analysis; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers