The Phenotypic and Functional Diversity of Tissue Tregs, and Their Role in Chronic Viral Infections

Abstract: 

Regulatory T cells (Tregs) are a subset of CD4+ T cells characterized by the expression of the transcription factor FoxP3. While Tregs are known to suppress immune cells to mediate immune responses, they exhibit location-specific functions across lymphoid and non-lymphoid tissues. This review examines the factors that influence location-specific functions of Treg phenotypes. While Tregs share some common characteristics, their roles are dependent on a range of tissue-specific factors. Exposure to varied stimuli across tissue environments, such as cytokines that act through distinct signaling pathways, as well as diverse cell-to-cell interactions, influence gene expression and drive differential behavior of Tregs. Additionally, Tregs play crucial roles in chronic viral infections, where they balance the facilitation of protective immune activity against foreign antigens with the need to prevent immunopathology, thereby allowing viral persistence. Through analysis of whole genome sequences, the role of Tregs in chronic norovirus infections was investigated. There was an accumulation of mutations in viral T cell epitopes over time in chronic infections, indicating that the virus better evades recognition by immune cells. This suggests the role of Tregs in suppressing antiviral immunity, while dampening pathogen-induced immunopathology. An understanding of the tissue-specific adaptations of Treg populations and their behavior in viral infections can inform novel therapies targeting Tregs for diseases and chronic infections in specific tissues.