title: CpG pretreatment enhances antiviral T-cell immunity against cytomegalovirus.
abstract: Major histocompatibility complex class I-restricted T-cell immunity is essential to control infection with cytomegalovirus (CMV), a clinically important virus that causes significant disease in immunocompromised individuals. Cross-presentation is considered the primary mode of antigen presentation to generate protective antiviral CD8⁺ T-cell immunity. Herpesviruses, including CMV, encode numerous proteins that interfere with direct antigen presentation, leading to the paradigm that T-cell immunity to these pathogens necessitates cross-presentation. However, the antigen presentation requirements needed to generate a protective T-cell response to CMV remain unknown. Here, we show that a fully functional antiviral CD8⁺ T-cell response can be generated in a system where cross-presentation is shut down by pretreatment with CpG. Notably, in this setting, CD8⁺ T cells demonstrate accelerated control of infection, and organ pathology is limited. These data indicate that protective antiviral T-cell immunity to CMV is generated by direct presentation and can be enhanced by pretreatment with CpG.
authors.affiliation: Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Crawley, WA, Australia.
authors.forename: Monique L
authors.initials: ML
authors.lastname: Ong
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Wikstrom
authors.forename: Peter
authors.initials: P
authors.lastname: Fleming
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Estcourt
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hertzog
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Hill
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Andoniou
authors.forename: Mariapia A
authors.initials: MA
authors.lastname: Degli-Esposti
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D045142:Cross-Priming / Q000276:immunology; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy*; D016867:Immunocompromised Host / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology / Q000821:virology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides