Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites
By Brahma V. Kumar, Wenji Ma, Michelle Miron, Tomer Granot, Rebecca S Guyer, Dustin J Carpenter, T. Senda, Xiaoyun Sun, S. Ho, H. Lerner and 3 more. Cell Reports, 2017
967 citations recorded by the source corpus.
SUMMARY Tissue-resident memory T cells (TRM) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRM remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells comprise a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69−TEM cells in tissues and circulation, and defines human TRM based on homology to the transcriptional profile of mouse CD8+TRM. Human TRM in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced proliferation compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/2df020b366030b1bd68fd79e0574e8a61c3f6d96
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In Immunology
Citations in the corpus
- Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy (2019, background): “Two of these clusters were highly enriched for the cytotoxic program (#26, 4), thus reminiscent of the Trm poised for cytotoxic functions recently described in the skin (Cheuk et al., 2017).”
- Human T cell development, localization, and function throughout life (2018, background): “Moreover, human Trm cells express surface receptors known to potently inhibit T cell function including PD-1, LAG3, and CTLA-4 (Hombrink et al., 2016; Kumar et al., 2017; Woon et al., 2016), and also CD101 (Kumar et al., 2017), a molecule associated with inhibition of proliferation (Soares et al., 1”
- CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment (2019, result): “While a significant amount of this research has been done on Trms in skin, some data shows that analysis of Trms across various tissues obtained from humans retain similar phenotypes, particularly in CD8 Trms (164).”
- Cross-tissue immune cell analysis reveals tissue-specific features in humans (2022, background): “TCR clone sharing between memory subtypes of CD8 T cells suggests their origin from a common precursor, or their differentiation or conversion during migration or maintenance, such as conversion of TEM cells to TRM cells (56).”