Single cell transcriptomics resolves activation dynamics and cellular states of human blood and tissue T cells
| العنوان: | Single cell transcriptomics resolves activation dynamics and cellular states of human blood and tissue T cells |
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| المؤلفون: | Peter Anthony Szabo, Hanna M Levitin, Michelle Miron, Mark E Snyder, Takashi Senda, Jinzhou Yuan, Yim Ling Chen, Erin C Bush, Pranay Dogra, Puspa Thapa, Peter A Sims, Donna L Farber |
| المصدر: | The Journal of Immunology. 202:60.5-60.5 |
| بيانات النشر: | The American Association of Immunologists, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | T cells persist as heterogeneous subsets throughout the body and are essential in mounting protective immune responses. In healthy humans, most of our knowledge of T cell activation derives from sampling the peripheral blood and therefore the transcriptional states of tissue T cells, their functional responses to stimulation, and how they relate to T cells in blood have been poorly defined. Here, we profile the activation dynamics of T cells isolated from human lungs (LG), lymph nodes (LN), bone marrow (BM) and blood following TCR-stimulation by single cell RNA-sequencing (scRNA-seq). Analysis of >50,000 individual resting and activated T cells using clustering and new factorization methods reveals lineage-specific gene expression signatures and discrete activation trajectories in all tissues. Between sites, T cells from LG and LN are most distinct, while blood T cells are most similar to those in BM but persist in a more activated basal state. We identify a common transcriptional profile of tissue T cells and detect trace numbers of these cells in the blood. We also define cellular states for resting and activated T cells across tissues, including an interferon-induced state in CD4+ T cells and distinct effector states specific to CD8+ T cells, and uncover new markers of T cell activation that may be central to T cell function. Importantly, we demonstrate that the T cell activation states resolved here serve as a new baseline for defining T cell dysfunction in disease, revealing novel insights into T cell states among tumor-infiltrating lymphocytes from previous studies. Our investigation couples scRNA-seq with new analysis methods to define the activation dynamics of human T cells from disparate anatomical sites on a single cell level. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::774d4cac6bce771ef6fd8b9ad86823e5 https://doi.org/10.4049/jimmunol.202.supp.60.5 |
| رقم الأكسشن: | edsair.doi...........774d4cac6bce771ef6fd8b9ad86823e5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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