Mucosal T-cell responses to chronic viral infections: Implications for vaccine design

Abstract Mucosal surfaces that line the respiratory, gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment. Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses. Numerous pathogenic viruses, including herpesviruses and retroviruses, exploit this environment to establish chronic infection. Effector and regulatory T-cell populations, including effector and resident memory T cells, play instrumental roles in mediating the transition from acute to chronic infection, where a degree of viral replication is tolerated to minimize immunopathology. Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses. In this review, we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa. We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies: not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.