Coxsackievirus B3 elicits a sex-specific CD8 ⁺ T cell response in female mice

Sex is a significant contributor to the outcome of human infections. Males are frequently more susceptible to viral, bacterial, and fungal infections, which is often attributed to a weaker immune response. 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-specific 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 CD11a hi CD62L lo CD8 + T cells in female mice, indicative of activation. Further, 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 is viral-specific and not due to bystander activation. These data demonstrate that CVB3 induces a sex-dependent CD8 + T cell response and highlight the importance of sex-specific immune responses to viral pathogens.