title: Interferons mediate terminal differentiation of human cortical thymic epithelial cells.
abstract: In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-beta) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-beta induction. Finally, we demonstrated that recombinant IFN-alpha, IFN-beta, or IFN-gamma was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections.
authors.affiliation: Laboratoire d'Immunobiologie Fondamentale et Clinique, INSERM U503, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Vidalain
authors.forename: David
authors.initials: D
authors.lastname: Laine
authors.forename: Yona
authors.initials: Y
authors.lastname: Zaffran
authors.forename: Olga
authors.initials: O
authors.lastname: Azocar
authors.forename: Christine
authors.initials: C
authors.lastname: Servet-Delprat
authors.forename: T Fabian
authors.initials: TF
authors.lastname: Wild
authors.forename: Chantal
authors.initials: C
authors.lastname: Rabourdin-Combe
authors.forename: Hélène
authors.initials: H
authors.lastname: Valentin
mesh_terms: D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D008459:Measles virus / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000378:metabolism; D011994:Recombinant Proteins; D013950:Thymus Gland / Q000166:cytology* / Q000821:virology; D014162:Transfection
chemical_list: D007370:Interferon Type I; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma