A virtual memory T cell spectrum
Virtual memory T (TVM) cells that acquire a memory phenotype in the absence of foreign antigen are believed to develop in response to self-antigen exposure, but their roles in protective immunity against foreign pathogens are not well understood. Using specific pathogen–free mice infected with influenza A virus, Hou et al. demonstrate that TVM cells rapidly infiltrate the lungs in a CXCR3-dependent manner, where they expand and promote early viral control. Compared with naïve T cells, TVM cells more efficiently gave rise to resident memory cells, with CCR2+ and CCR2− subsets poised for effector and memory responses, respectively. These results demonstrate that TVM cells undergo functional specialization and highlight how self-reactive T cells can productively contribute to antigen-specific responses against invading pathogens.
Abstract
A primary immune response is 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, 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 influenza infection, TVM cells rapidly infiltrate the lungs in the first day after infection and promote early viral control. TVM 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 TVM cells bridge innate reaction and adaptive memory directly in the infected tissue.
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