Virtual memory T cells orchestrate extralymphoid responses conducive to resident memory

A spectrum of virtual memory T cells

Virtual memory T (TMV) cells that acquire a memory phenotype in the absence of foreign antigen are believed to develop in response to exposure to the autoantigen, but their roles in protective immunity against foreign pathogens are not well understood. Using mice free of specific pathogens infected with influenza A virus, Hou et al. show that TMV the cells rapidly infiltrate the lungs in a CXCR3-dependent manner, where they grow and promote early viral control. Compared to naive T cells, TMV cells more efficiently gave birth to resident memory cells, with CCR2+ and CCR2 subsets ready for effector and memory responses, respectively. These results demonstrate that TMV cells undergo functional specialization and demonstrate how autoreactive T cells can productively contribute to antigen-specific responses against invading pathogens.


A primary immune response is initiated in the secondary lymphoid organs. CD8 virtual memory+ T (TMV) are inexperienced T cells with antigen of a central memory phenotype, acquired by self-antigen homeostatic proliferation. Unexpectedly, we find that TMV cells are made up of CCR2+ and CCR2 subsets which differentially develop a spectrum of effector and memory functions directly in the tissue. During a primary influenza infection, TMV the cells quickly infiltrate the lungs on the first day after infection and promote early viral control. TMV cells that recognize the viral antigen are retained in the tissue, grow clonally independent of secondary lymphoid organs, and give rise to memory cells resident in the tissue. By orchestrating an extralymphoid primary response, heterogeneous TMV cells connect the innate response and adaptive memory directly in the infected tissue.

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