title: Macrophage cultures are susceptible to lytic productive infection by endothelial-cell-propagated human cytomegalovirus strains and present viral IE1 protein to CD4+ T cells despite late downregulation of MHC class II molecules.
abstract: The contribution of CD4(+) T cells to control of human cytomegalovirus (HCMV) has been shown and infected tissue macrophages might contribute to this response by antigen presentation. As shown previously, CD4(+) T cells recognize HCMV immediate-early antigen IE1 on glioblastoma cells manipulated to express MHC class II molecules. Here, the possible interference of virus-induced MHC class II downmodulation with the presentation of IE1 by natural target cells was analysed. The capacity of IE1-specific CD4(+) T-cell clones to recognize HCMV-infected monocyte-derived macrophages was tested. Various HCMV strains were used to achieve efficient infection of macrophages. Activation of CD4(+) T cells by infected macrophages was evaluated at different time points after infection. Endothelial-cell-adapted HCMV strains efficiently infected cultured human macrophages. However, the immediate-early and early phases of replication were prolonged. Infected cells entered the late replication phase only after 3 days of infection, which was associated with downmodulation of MHC class II molecules at the surface of infected cells. Strong stimulation of IE1-specific CD4(+) T cells resulted from endogenous de novo antigen production and presentation by infected macrophages during the first 3 days of virus replication, despite MHC class II downmodulation in the late replication phase. Therefore, infected macrophages are assumed to contribute to the antiviral immune response in infected organs.
authors.affiliation: Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sinzger
authors.affiliation: Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Eberhardt
authors.affiliation: Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Yolaine
authors.initials: Y
authors.lastname: Cavignac
authors.affiliation: Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Weinstock
authors.affiliation: Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kessler
authors.affiliation: Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jahn
authors.affiliation: INSERM U563, CPTP, IFR 30, CHU PURPAN, 31024 Toulouse Cedex, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Davignon
mesh_terms: D017951:Antigen Presentation; D000956:Antigens, Viral / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000209:etiology; D003588:Cytopathogenic Effect, Viral; D015536:Down-Regulation; D042783:Endothelial Cells / Q000821:virology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D014764:Viral Proteins / Q000276:immunology*; D014776:Virus Cultivation; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D000949:Histocompatibility Antigens Class II; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D014764:Viral Proteins