Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Cell. 2020 Dec 23;183(7):1946-1961.e15. doi: 10.1016/j.cell.2020.11.019. Epub 2020 Dec 10.
Lymphocyte migration is essential for adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies have been restricted to immunological analyses of blood and various tissues. To address this knowledge gap, we used an integrated approach to characterize tissue-emigrant lineages in thoracic duct lymph (TDL). The most prevalent immune cells in human and non-human primate efferent lymph were T cells. Cytolytic CD8 T cell subsets with effector-like epigenetic and transcriptional signatures were clonotypically skewed and selectively confined to the intravascular circulation, whereas non-cytolytic CD8 T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Moreover, these anatomically distinct gene expression profiles were recapitulated within individual clonotypes, suggesting parallel differentiation programs independent of the expressed antigen receptor. Our collective dataset provides an atlas of the migratory immune system and defines the nature of tissue-emigrant CD8 T cells that recirculate via TDL.
淋巴细胞的迁移对于适应性免疫监视至关重要。然而，我们目前对这一过程的了解还很基础，因为大多数人类研究都局限于对血液和各种组织的免疫学分析。为了解决这一知识空白，我们采用了一种综合方法来描述胸导管淋巴（TDL）中的组织迁出谱系。在人和非人类灵长类动物的流出淋巴中，最常见的免疫细胞是 T 细胞。具有效应细胞样表观遗传和转录特征的细胞毒性 CD8 T 细胞亚群在克隆型上倾斜，选择性地局限于血管内循环，而具有干细胞样表观遗传和转录特征的非细胞毒性 CD8 T 细胞亚群在组织和 TDL 中占优势。此外，这些在解剖学上不同的基因表达谱在单个克隆型内重现，表明独立于表达的抗原受体存在平行的分化程序。我们的综合数据集提供了一个迁移免疫系统图谱，并定义了通过 TDL 再循环的组织迁出 CD8 T 细胞的性质。
