To establish a foundation for analyzing T cell activation and functional status, Szabo et al. utilized single cell RNA-sequencing (scRNAseq) for cataloging the heterogeneity and functional status of resting and stimulated T cells from healthy human blood, lymphoid, and mucosal tissues. Distinct CD4+/CD8+ T cell expression signatures distinguished blood and tissue subsets, while conserved signatures identified CD4+ T cell activation states across all tested tissues. In tumors, scRNAseq identified cytotoxic T cells, cytokine-producing CD8+ T cells, Tregs, and resting CD4+ T cells as predominant phenotypes, however, activated CD4+ T cells were absent.
Contributed by Samuel Goldman
Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8(+) T cells and an interferon-response state for CD4(+) T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8(+) compared to CD4(+) T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.