Virtual memory T-cells orchestrate extra-lymphoid responses conducive to resident memory

A primary immune response is typically initiated in secondary lymphoid organs. Virtual memory CD8+ T (TVM) cells are antigen-inexperienced T cells of a central-memory phenotype, acquired through self antigen-driven homeostatic proliferation. Unexpectedly, here we find that, TVM 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 flu infection, TVM cells rapidly infiltrate the lung in the first day and execute early viral control. TVM cells that recognize viral antigen are retained in the tissue, clonally expand independent of secondary lymphoid organs, and preferentially give rise to tissue-resident memory cells. By orchestrating an extra-lymphoid primary response, heterogenous TVM cells bridge innate reaction and adaptive memory directly in the infected tissue. Differential expression analysis between CCR2+ and CCR2- virtual memory CD8+ T cells