CpG pretreatment enhances antiviral T-cell immunity against cytomegalovirus

Blood. 2013 Jul 4;122(1):55-60. doi: 10.1182/blood-2012-12-471227. Epub 2013 May 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigen Presentation / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology*
  • Cross-Priming / immunology
  • Cytomegalovirus / growth & development
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / therapy*
  • Immunocompromised Host / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Oligodeoxyribonucleotides / pharmacology*
  • Spleen / immunology
  • Spleen / virology

Substances

  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides