PMID- 10756053 OWN - NLM STAT- MEDLINE DCOM- 20000518 LR - 20190508 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 74 IP - 9 DP - 2000 May TI - Consequences of Fas-mediated human dendritic cell apoptosis induced by measles virus. PG - 4387-93 AB - 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. FAU - Servet-Delprat, C AU - Servet-Delprat C AD - Immunobiologie Fondamentale et Clinique, INSERM U503, ENS Lyon, 69 364 Lyon cedex 07, France. cservet@ens-lyon.fr FAU - Vidalain, P O AU - Vidalain PO FAU - Azocar, O AU - Azocar O FAU - Le Deist, F AU - Le Deist F FAU - Fischer, A AU - Fischer A FAU - Rabourdin-Combe, C AU - Rabourdin-Combe C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (CD40 Antigens) RN - 0 (fas Receptor) SB - IM MH - *Apoptosis MH - CD40 Antigens/immunology MH - Coculture Techniques MH - Dendritic Cells/cytology/immunology/*virology MH - Humans MH - Measles virus/immunology/*physiology MH - T-Lymphocytes/immunology/virology MH - Virus Replication MH - fas Receptor/*metabolism PMC - PMC111955 EDAT- 2001/02/07 11:00 MHDA- 2001/02/07 11:01 PMCR- 2000/05/01 CRDT- 2001/02/07 11:00 PHST- 2001/02/07 11:00 [pubmed] PHST- 2001/02/07 11:01 [medline] PHST- 2001/02/07 11:00 [entrez] PHST- 2000/05/01 00:00 [pmc-release] AID - 1669 [pii] AID - 10.1128/jvi.74.9.4387-4393.2000 [doi] PST - ppublish SO - J Virol. 2000 May;74(9):4387-93. doi: 10.1128/jvi.74.9.4387-4393.2000.