Navigating in Deep Waters: How Tissue Damage and Inflammation Shape Effector and Memory CD8⁺ T Cell Responses

Memory CD8⁺ T cells promote protective immunity against viruses or cancer. Our field has done a terrific job identifying how CD8⁺ T cell memory forms in response to Ag. However, many studies focused on systems in which inflammation recedes over time. These situations, while relevant, do not cover all situations in which CD8⁺ T cell memory is relevant. It is increasingly clear that CD8⁺ T cells with a memory phenotype form in response to infections with extensive or prolonged tissue inflammation, for example, influenza, herpes, and more recently, COVID-19. In these circumstances, inflammatory mediators expectedly affect forming memory CD8⁺ T cells, especially in tissues in which pathogens establish. Notwithstanding recent important discoveries, many outstanding questions on how inflammation shapes CD8⁺ T cell memory remain unanswered. We will discuss, in this review, what is already known and the next steps to understand how inflammation influences CD8⁺ T cell memory.