Tissue adaptation and clonal segregation of human memory T cells in barrier sites.
Maya Meimei Li PoonDaniel P CaronZicheng WangSteven B WellsDavid ChenWenzhao MengPeter A SzaboNora LamMasaru KubotaRei MatsumotoAdeeb RahmanEline T Luning PrakYufeng ShenPeter A SimsDonna L FarberPublished in: Nature immunology (2023)
T lymphocytes migrate to barrier sites after exposure to pathogens, providing localized immunity and long-term protection. Here, we obtained blood and tissues from human organ donors to examine T cells across major barrier sites (skin, lung, jejunum), associated lymph nodes, lymphoid organs (spleen, bone marrow), and in circulation. By integrating single-cell protein and transcriptome profiling, we demonstrate that human barrier sites contain tissue-resident memory T (T RM ) cells that exhibit site-adapted profiles for residency, homing and function distinct from circulating memory T cells. Incorporating T cell receptor and transcriptome analysis, we show that circulating memory T cells are highly expanded, display extensive overlap between sites and exhibit effector and cytolytic functional profiles, while T RM clones exhibit site-specific expansions and distinct functional capacities. Together, our findings indicate that circulating T cells are more disseminated and differentiated, while T RM cells exhibit tissue-specific adaptation and clonal segregation, suggesting that strategies to promote barrier immunity require tissue targeting.
Keyphrases
- endothelial cells
- single cell
- induced apoptosis
- working memory
- bone marrow
- lymph node
- gene expression
- induced pluripotent stem cells
- pluripotent stem cells
- rna seq
- cell cycle arrest
- healthcare
- oxidative stress
- patient safety
- endoplasmic reticulum stress
- signaling pathway
- regulatory t cells
- high throughput
- quality improvement
- drug delivery
- cancer therapy
- neoadjuvant chemotherapy
- type iii