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Journal of Virology, July 2002, p. 6415-6424, Vol. 76, No. 13
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.13.6415-6424.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Interferons Mediate Terminal Differentiation of Human Cortical Thymic Epithelial Cells
Pierre-Olivier Vidalain,1 David Laine,1 Yona Zaffran,1 Olga Azocar,1 Christine Servet-Delprat,1 T. Fabian Wild,2 Chantal Rabourdin-Combe,1 and Hélène Valentin1*
Laboratoire d'Immunobiologie Fondamentale et Clinique, INSERM U503,1
Immunity and Vaccination, INSERM U404, 69365 Lyon Cedex 07, France2
Received 11 December 2001/
Accepted 28 March 2002
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-ß) 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-ß induction. Finally, we demonstrated that recombinant IFN-
, IFN-ß, or IFN-
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.
* Corresponding author. Mailing address: INSERM U503, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France. Phone: (33) 4 37 28 23 77. Fax: (33) 4 37 28 23 41. E-mail:
valentin{at}cervi-lyon.inserm.fr.
Journal of Virology, July 2002, p. 6415-6424, Vol. 76, No. 13
0022-538X/02/$04.00+0 DOI: 10.1128/JVI.76.13.6415-6424.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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