title: Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection.
abstract: Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by CTLA-4-expressing T cells and constitutes an important mediator of peripheral immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication expressed higher levels of IDO mRNA than noninfected cells when stimulated with gamma interferon or when cocultured with activated T cells. In infected chimpanzees, hepatic IDO expression decreased in animals that cured the infection, while it remained high in those that progressed to chronicity. For both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated directly. Induction of IDO may dampen T-cell reactivity to viral antigens in chronic HCV infection.
authors.affiliation: Division of Gene Therapy and Hepatology, Center for Applied Medical Research, CIMA, Avenida Pío XII 55, 31008 Pamplona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Larrea
authors.forename: José I
authors.initials: JI
authors.lastname: Riezu-Boj
authors.forename: Lucía
authors.initials: L
authors.lastname: Gil-Guerrero
authors.forename: Noelia
authors.initials: N
authors.lastname: Casares
authors.forename: Rafael
authors.initials: R
authors.lastname: Aldabe
authors.forename: Pablo
authors.initials: P
authors.lastname: Sarobe
authors.forename: María P
authors.initials: MP
authors.lastname: Civeira
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
authors.forename: Christine
authors.initials: C
authors.lastname: Rollier
authors.forename: Babs
authors.initials: B
authors.lastname: Verstrepen
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrás-Cuesta
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D060908:CTLA-4 Antigen; D015331:Cohort Studies; D015971:Gene Expression Regulation, Enzymologic; D006526:Hepatitis C / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger