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American Heart Association

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Final ID: Mo126

A sex-specific CD4+ T cell response limits Coxsackievirus B pathogenesis in mice.

Abstract Body: Coxsackievirus B3 (CVB3) is an enteric virus that is a primary cause of inflammation of the heart muscle, known as viral myocarditis. Viral myocarditis is a significant cause of heart failure, and nearly 40,000 cases are reported each year. Unfortunately, approximately 5% of CVB3 infections are fatal. Unfortunately, no vaccines or drugs are available for this virus. Interestingly, there is a sex bias in viral myocarditis where men are more susceptible than women. Unfortunately, the underlying basis for the sex bias in infection is incompletely understood. We recently determined that T cells play an essential role in CVB3 clearance using a novel oral inoculation mouse model. Here, we show a sex difference in the CD4+ T cell response to CVB3 that is important in limiting viral pathogenesis. We found that CVB3 induced CD4+ cell expansion in female mice but not in male mice. CVB3 infection also led to the expansion of CD62Llo CD4+ T cells in the mesenteric lymph node and spleen of female but not male mice as early as five days post-inoculation, indicative of activation. Using a recombinant CVB3 virus expressing a model CD4+ T cell epitope, we found that the expansion of CD4+ T cells in females is viral-specific and not due to bystander activation. Finally, the depletion of CD4+ T cells before infection led to enhanced mortality, indicating that CD4+ T cells protect against CVB3 in female mice. We are also currently investigating the impact of CD4+ T cell subtypes, and the role of intestinal T cells play in limiting intestinal CVB3 replication and dissemination. These data demonstrate that CVB3 induces a CD4+ T cell response in female mice and highlight the importance of sex-specific immune responses to viral pathogens.
  • Robinson, Christopher  ( Indiana University School of Medicine , Zionsville , Indiana , United States )
  • Pattnaik, Aryamav  ( Indiana University School of Medicine , Zionsville , Indiana , United States )
  • Dhalech, Adeeba  ( Indiana University School of Medicine , Zionsville , Indiana , United States )
  • Condotta, Stephanie  ( Indiana University School of Medicine , Zionsville , Indiana , United States )
  • Corn, Caleb  ( Indiana University School of Medicine , Zionsville , Indiana , United States )
  • Richer, Martin  ( Indiana University School of Medicine , Zionsville , Indiana , United States )
  • Snell, Laura  ( Indiana University School of Medicine , Zionsville , Indiana , United States )
  • Author Disclosures:
    Christopher Robinson: DO NOT have relevant financial relationships | Aryamav Pattnaik: No Answer | Adeeba Dhalech: No Answer | Stephanie Condotta: No Answer | Caleb Corn: No Answer | Martin Richer: No Answer | Laura Snell: DO NOT have relevant financial relationships
Meeting Info:

Basic Cardiovascular Sciences

2024

Chicago, Illinois

Session Info:

Poster Session and Reception I

Monday, 07/22/2024 , 04:30PM - 07:00PM

Poster Session and Reception

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