Evolving role of CD8+ tissue-resident memory T cells in autoimmune and immune mediated inflammatory diseases: linking pathogenesis to therapeutic approaches

Abstract

Memory CD8+ T cells provide accelerated protection against intracellular pathogens and tumors. Circulating memory T cells recirculate through blood and lymphoid tissues and can enter peripheral tissues during infection, whereas tissue-resident memory T cells (TRM), persist long-term in peripheral tissues, often at sites of previous pathogen infection where they can rapidly respond to antigen re-exposure. Although CD8+ TRM cells lodge long-term within tissues, they are not stationary; many survey their local environment. CD8+ TRM cells respond rapidly to antigen encounter by producing cytokines. These cytokines stimulate epithelial and innate immune cells to produce antimicrobial peptides and chemokines promoting recruitment of circulating leukocytes. Their localization within tissues provides protection against local reinfection, but persistent or dysregulated CD8+ TRM cells may also sustain tissue inflammation and promote local disease recurrence in autoimmune and immune-mediated inflammatory diseases. Here, we review the mechanisms that establish and maintain CD8+ TRM cells; evaluate evidence for their pathogenic roles in inflammatory disease; and discuss current and emerging therapeutic strategies for targeting pathogenic CD8+ TRM cells.