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.
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.
Sinzger
Christian
C
Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Eberhardt
Kathrin
K
Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Cavignac
Yolaine
Y
Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Weinstock
Christof
C
Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Kessler
Tobias
T
Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Jahn
Gerhard
G
Institut für Medizinische Virologie, Universitätsklinikum Tübingen, Tübingen, Germany.
Davignon
Jean-Luc
JL
INSERM U563, CPTP, IFR 30, CHU PURPAN, 31024 Toulouse Cedex, France.
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
D000956:Antigens, Viral; D000949:Histocompatibility Antigens Class II; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D014764:Viral Proteins