Herpes simplex inhibits the capacity of lymphoblastoid B cell lines to stimulate CD4+ T cells.
HSV establish a lifelong persistent infection in their host even among immunocompetent persons. The viruses use a variety of immune evasion strategies, presumably to assist persistent replication in the human host. We have observed that infection of human B lymphoblastoid cells (B-LCL) by HSV resulted in a strong inhibition of their ability to induce CD4(+) T cell clone proliferation and cytokine secretion. This inhibitory effect occurs in a variety of both HSV- and HIV-specific clones from three different patients. The inhibition is observed when the Ag is provided either as a soluble protein or as a synthetic peptide and is not associated with detectable down-modulation of the MHC class II molecules or costimulatory molecules. Expression of the HSV-1 unique sequence 1 gene (US1) is necessary and sufficient to induce this inhibition of APC function. US1 gene expression also made B-LCL less susceptible to CD4(+) T cell-mediated lysis. These data indicate a novel immune evasion strategy by HSV-1 in which Ag-processing cells that become infected by HSV-1 are inhibited in their ability to induce subsequent CD4(+) T cell activation.
Barcy
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S
Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
Corey
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L
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000378:metabolism; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002461:Cell Line, Transformed / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D017781:Genes, Immediate-Early / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C057294:ICP22 protein, human herpesvirus 1; C105843:ICP47 protein, Herpes simplex virus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C078424:EUS1 protein, Equine herpesvirus 1