The multifaceted role of CD4+ T cells in CD8+ T cell memory

Following immunization, CD4+ T cells promote the induction of a robust primary CD8+ T cell response through numerous mechanisms, including licensing of dendritic cells (DCs) and promoting the interaction between DCs and CD8+ T cells.CD4+ T cells regulate the secondary responsiveness of CD8+ T cells during immunization through suppression of TNF-related apoptosis-inducing ligand (TRAIL) through a process dependent on licensing of DCs to produce interleukin-15 (IL-15) and autocrine secretion of IL-2 by CD8+ T cells.Following infection, CD4+ T cell help is necessary for the induction of a memory CD8+ T cell pool capable of mediating protective immunity but is largely dispensable for a robust primary response.Regulatory T (TReg) cells act during the resolution phase of infection to protect CD8+ T cells from inflammatory signals and promote the survival of a CD8+ T cell pool capable of robustly expanding upon secondary infection.CD4+ T cell help promotes the induction of tissue-resident memory CD8+ T cells during mucosal infection through guidance of CD8+ T cells into a microenvironment where they can become exposed to the signals necessary for their continued maintenance within the tissue.During chronic infection, effector CD4+ T cells support the maintenance of functional CD8+ T cells through secretion of IL-21, whereas TReg cells dampen the CD8+ T cell response through suppression of DCs.