Immune synapses formed with measles virus-infected dendritic cells are unstable and fail to sustain T cell activation.
Interaction with dendritic cells (DCs) is considered as central to immunosuppression induced by viruses, including measles virus (MV). Commonly, viral infection of DCs abrogates their ability to promote T cell expansion, yet underlying mechanisms at a cellular level are undefined. We found that MV-infected DCs only subtly differed from LPS-matured with regard to integrin activation, acquisition of a migratory phenotype and motility. Similarly, the organization of MV-DC/T cell interfaces was consistent with that of functional immune synapses with regard to CD3 clustering and MHC class II surface recruitment. The majority of MV-DC/T cell conjugates was, however, unstable and only promoted abortive T cell activation. Thus, MV-infected DCs retain activities required for initiating, but not sustaining T cell conjugation and activation. This is partially rescued if surface expression of the MV glycoproteins on DCs is abolished by infection with a recombinant MV encoding VSV G protein instead, indicating that these contribute directly to synapse destabilization and thereby act as effectors of T cell inhibition.
Shishkova
Yoanna
Y
University of Würzburg, Institute for Virology and Immunobiology, Versbacher Street 7, D-97078 Würzburg, Germany.
Harms
Harry
H
Krohne
Georg
G
Avota
Elita
E
Schneider-Schaulies
Sibylle
S
D002448:Cell Adhesion; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005802:Genes, MHC Class II; D006023:Glycoproteins / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D018613:Microscopy, Confocal; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018116:Vesiculovirus / Q000235:genetics
D006023:Glycoproteins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D016023:Integrins; D008070:Lipopolysaccharides; D019204:GTP-Binding Proteins