Dhalech, Adeeba H.Condotta, Stephanie A.Pattnaik, AryamavCorn, CalebRicher, Martin J.Robinson, Christopher M.2024-03-122024-03-122023-09-05Dhalech AH, Condotta SA, Pattnaik A, Corn C, Richer MJ, Robinson CM. Coxsackievirus B3 elicits a sex-specific CD8+ T cell response which protects female mice. PLoS Pathog. 2023;19(9):e1011465. Published 2023 Sep 5. doi:10.1371/journal.ppat.1011465https://hdl.handle.net/1805/39201Sex is a significant contributor to the outcome of human infections. Males are frequently more susceptible to viral, bacterial, and fungal infections, often attributed to weaker immune responses. In contrast, a heightened immune response in females enables better pathogen elimination but leaves females more predisposed to autoimmune diseases. Unfortunately, the underlying basis for sex-specific immune responses remains poorly understood. Here, we show a sex difference in the CD8+ T cell response to an enteric virus, Coxsackievirus B3 (CVB3). We found that CVB3 induced expansion of CD8+ T cells in female mice but not in male mice. CVB3 also increased the proportion and number of CD11ahiCD62Llo CD8+ T cells in female mice, indicative of activation. This response was independent of the inoculation route and type I interferon. Using a recombinant CVB3 virus expressing a model CD8+ T cell epitope, we found that the expansion of CD8+ T cells in females is viral-specific and not due to bystander activation. Finally, the depletion of CD8+ T cells, prior to infection, led to enhanced mortality, indicating that CD8+ T cells are protective against CVB3 in female mice. These data demonstrate that CVB3 induces a CD8+ T cell response in female mice and highlight the importance of sex-specific immune responses to viral pathogens.en-USAttribution 4.0 InternationalViral antigensEnterovirus infectionsInterferon type IOrthopoxvirusArticle