Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner

Area of Science:

• Immunology
• Cell Biology

Background:

• Virtual memory (VM) cells are a CD8 T-cell subset with memory phenotype.
• Previously, VM cells were thought to arise from homeostatic proliferation (HP) in lymphopenic environments.

Purpose of the Study:

• To investigate the ongoing HP in lymphoreplete mice.
• To explore the functional capacity of VM cells in protective immunity.
• To identify analogous VM-like cells in humans.

Main Methods:

• Analysis of CD8 T-cell populations in lymphoreplete mice.
• Transcriptional profiling of VM cells.
• Investigation of IL-15 dependency for VM cell function.
• Phenotypic and functional analysis of human cells.

Main Results:

• Homeostatic proliferation (HP) is ongoing in lymphoreplete mice, influenced by naive CD8 T-cell affinity for self-antigen and peripheral IL-15.
• VM cells possess the capacity for antigen non-specific bystander killing, dependent on IL-15.
• A human VM-like cell population accumulates with age, traffics to the liver, and exhibits bystander protective functions.

Conclusions:

• VM cell development and function are linked to ongoing homeostatic proliferation and IL-15 signaling.
• VM cells play a role in protective immunity through bystander killing.
• Age-associated human VM-like cells share functional similarities with mouse VM cells, suggesting a conserved role in immunity.