A single-cell reference map for human blood and tissue T cell activation reveals functional states in health and disease

ABSTRACT

Human T cells coordinate adaptive immunity by localization in diverse tissue sites, though blood T cells are the most readily studied. Here, we used single-cell RNA-seq to define the functional responses of T cells isolated from human lungs, lymph nodes, bone marrow, and blood to TCR-stimulation. We reveal how human T cells in tissues relate to those in blood, and define activation states for CD4⁺ and CD8⁺T cells across all sites, including an interferon-response state for CD4⁺T cells and distinct effector states for CD8⁺T cells. We further show how profiles of individual tumor-associated T cells can be projected onto this healthy reference map, revealing their functional state.