Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
PLoS Pathog. 2023 Sep 5;19(9):e1011465. doi: 10.1371/journal.ppat.1011465. eCollection 2023 Sep.
Sex 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.
性别是影响人类感染结果的重要因素。男性通常更容易感染病毒、细菌和真菌感染，这通常归因于较弱的免疫反应。相比之下，女性更强的免疫反应有助于更好地清除病原体，但也使女性更容易患自身免疫性疾病。不幸的是，性别特异性免疫反应的潜在基础仍知之甚少。在这里，我们展示了对肠道病毒柯萨奇病毒 B3 (CVB3) 的 CD8+T 细胞反应中的性别差异。我们发现 CVB3 诱导雌性小鼠而非雄性小鼠的 CD8+T 细胞扩增。CVB3 还增加了雌性小鼠中 CD11ahiCD62Llo CD8+T 细胞的比例和数量，表明其处于激活状态。这种反应独立于接种途径和 I 型干扰素。使用表达模型 CD8+T 细胞表位的重组 CVB3 病毒，我们发现雌性小鼠中 CD8+T 细胞的扩增是病毒特异性的，而不是由于旁邻激活。最后，在感染前耗尽 CD8+T 细胞会导致死亡率增加，表明 CD8+T 细胞对雌性小鼠 CVB3 具有保护作用。这些数据表明 CVB3 诱导雌性小鼠产生 CD8+T 细胞反应，并强调了性别特异性免疫反应对病毒病原体的重要性。
