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

How inflammation can affect memory CD8⁺ T cells.

This hypothetical scheme highlights the common relation between inflammatory signals and memory CD8⁺ T cells. Independent of location or nature of memory CD8⁺ T cells, low or no inflammation mostly hinders memory CD8⁺ T cell generation (including the input of effector cells needed for effector-to-memory conversion) and survival. Conversely, excessive inflammation usually diverts activated CD8⁺ T cells toward terminal-like phenotypes, consequently leading to increased population death; this is also true for existing memory CD8⁺ T cells, in which too high levels of proinflammatory signals lead to both a conversion to a effector-like phenotype and increased attrition. There is a likely sweet spot, where enough type 1 inflammatory signals promote effective priming of CD8⁺ T cells (together with TCR and costimulation), appropriate MP generation (both in circulation and in tissues), and efficient maintenance and reactivation of memory CD8⁺ T cells, either in the presence or not of secondary Ag. Manipulations of local and/or systemic inflammation should ideally shape the inflammatory environment to reach this hypothetical sweet spot, which may vary from tissue to tissue and from infection to infection. The figure was created with Biorender.com.