Single cell RNA-seq resolves lineage-specific activation dynamics of human blood and tissue T cells

Human T cells coordinate adaptive immunity and persist as heterogeneous subsets in tissues and circulation, yet the impact of localization on T cell function remains unclear. Here, we profile activation of T cells from human lungs, lymph nodes (LN), bone marrow (BM) and blood following TCR/CD3 stimulation by single cell RNA-seq. Analysis of >50,000 individual resting and activated T cells using new factorization methods reveals conserved lineage-specific gene expression signatures and activation trajectories across sites. CD4 T cells exhibit a transient intermediate activation state while CD8 T cells show an “all-off/all-on” activation pattern. Lung and LN T cells exhibit tissue-specific profiles, while blood T cells closely resemble those in BM. Our results define the lineage-specific activation dynamics of human T cells from different anatomical sites. Overall design: Here, we profile activation of T cells from human lungs, lymph nodes (LN), bone marrow (BM) and blood following TCR/CD3 stimulation by single cell RNA-seq.