CD8+ T cells modulate antigen-presenting cell function via Integrin-alpha E

Replication of virus in antigen presenting cells (APCs) can be beneficial for innate and adaptive immune activation, however it can become fatal if replication is not tightly regulated. Whether specific signals switch antiviral versus pro-viral programs in APCs remains unknown. Here, by using a genome wide association study (GWAS), we identified Integrin alpha-E (Itgae, CD103) as one major inducer of pro-viral activity in dendritic cells (DCs). Mechanistically, Itgae expressing CD8+ T cells or lymphoid DCs blocked e-cadherin homotypic interactions in APCs. Thereby AKT/NF-KB signaling was blocked and APCs could not initiate antiviral activity. Lack of Itgae enhanced AKT/NF-KB signaling in APCs and resulted in strong antiviral activity. In vivo, Itgae expression accelerated CD8+ T cell responses during acute and chronic viral infections and thereby influenced the outcome of infection. In conclusion, Itgae acts as trigger that allows CD8+ T cells to block the antiviral status in APCs and thereby modulates antiviral CD8+ T cell responses.