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Journal of Virology, May 2000, p. 4387-4393, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Consequences of Fas-Mediated Human Dendritic Cell Apoptosis Induced by Measles Virus

Christine Servet-Delprat,1,* Pierre-Olivier Vidalain,1 Olga Azocar,1 Françoise Le Deist,2 Alain Fischer,2 and Chantal Rabourdin-Combe1

Immunobiologie Fondamentale et Clinique, INSERM U503, ENS Lyon, 69 364 Lyon cedex 07,1 and Développement Normal et Pathologique du Système Immunitaire, INSERM U429, Hôpital Necker-Enfants Malades, 75 743 cedex 15 Paris,2 France

Received 27 September 1999/Accepted 21 January 2000

Mortality from measles virus (MV) infection is caused mostly by secondary infections associated with a pronounced immunosuppression. Dendritic cells (DCs) represent a major target of MV and could be involved in immunosuppression. In this study, human monocyte-derived DCs were used to demonstrate that DC apoptosis in MV-infected DC-T-cell cocultures is Fas mediated, whereas apoptotic T cells could not be rescued by blocking the Fas pathway. Two novel consequences of DC apoptosis after MV infection were demonstrated. (i) Fas-mediated apoptosis of DCs facilitates MV release, while CD40 activation enhances MV replication in DCs. Indeed, detailed studies of infectious MV release and intracellular MV nucleoprotein (NP) showed that inhibition of CD40-CD40L ligand interaction blocks NP synthesis. We conclude that the CD40 ligand expressed by activated T cells first enhances MV replication in DCs, and then Fas ligand produced by activated T cells induces Fas-mediated apoptosis of DCs, thus facilitating MV release. (ii) Not only MV-infected DCs but also bystander uninfected DCs undergo a maturation process confirmed by CD1a, CD40, CD80, CD86, CD83, and major histocompatibility complex type II labeling. The bystander maturation effect results from contact and/or engulfment of MV-induced apoptotic DCs by uninfected DCs. A model is proposed to explain how both a specific immune response and immunosuppression can simultaneously occur after MV infection through Fas-mediated apoptosis and CD40 activation of DCs.

* Corresponding author. Mailing address: INSERM U503, Immunobiologie Fondamentale et Clinique, ENS de Lyon, 69364 Lyon cedex 07, France. Phone: (33) 4 72 72 80 13. Fax: (33) 4 72 72 80 80. E-mail: cservet{at}ens-lyon.fr.

Journal of Virology, May 2000, p. 4387-4393, Vol. 74, No. 9
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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