Human lung tissue-resident memory CD8+ T cells are transcriptionally, epigenetically, and phenotypically diverse
| Autor: | Jennifer L Elliott, Kirsten N Kost, Kristiana H Lacetti, Jeronay K Thomas, M Elliott Williams, Cameron L Mattingly, Jenna L Lobby, Laurel A Lawrence, Jacob E Kohlmeier |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 208:182.21-182.21 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Tissue-resident memory CD8+ T cells (TRM) are strategically located in peripheral tissues, especially at mucosal surfaces, where they can provide protection against invading pathogenic microbes. In the lungs, TRM play a critical role in limiting disease and transmission of respiratory viruses; however, the heterogeneity present in TRM populations in the human lung remains largely unexplored. Here we show that human lungs harbor transcriptionally, epigenetically, and phenotypically distinct populations of memory CD8+ T cells expressing the tissue residency-associated markers CD69 and CD103. High-dimensional flow cytometry and single-cell RNA sequencing of memory CD8+ T cells isolated from human lungs shows that heterogeneity exists both between and within CD69+ CD103− and CD69+ CD103+ subsets, with transcriptional diversity among the CD69+ CD103− subset being most prominent. Single-cell ATACseq demonstrates that similar levels of epigenetic diversity exist between and within these different TRM subsets. However, flow cytometry and single-cell RNAseq of influenza- and SARS-CoV-2-specific lung TRM demonstrates that heterogeneity between CD69+ CD103− and CD69+ CD103+ subsets is largely eliminated when the cells are specific for a common antigen. Together, these data illuminate underappreciated and unexplored aspects of heterogeneity in TRM populations in humans. Supported by grants from NIH/NIAID (75N93019R00028) and NIH/NHLBI (R35 HL150803) |
| Databáze: | OpenAIRE |
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