Virtual memory T cells orchestrate extralymphoid responses conducive to resident memory

A primary immune response is initiated in secondary lymphoid organs. Virtual memory CD8(+) T (T-VM) cells are antigen-inexperienced T cells of a central memory phenotype, acquired through self-antigen-driven homeostatic proliferation. Unexpectedly, we find that T-VM cells are composed of CCR2(+) and CCR2(-) subsets that differentially elaborate a spectrum of effector- and memory-poised functions directly in the tissue. During a primary influenza infection, T-VM cells rapidly infiltrate the lungs in the first day after infection and promote early viral control. T-VM cells that recognize viral antigen are retained in the tissue, clonally expand independent of secondary lymphoid organs, and give rise to tissue-resident memory cells. By orchestrating an extralymphoid primary response, heterogenous T-VM cells bridge innate reaction and adaptive memory directly in the infected tissue.