| Title: |
Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets |
| Authors: |
FitzPatrick, MEB; Provine, NM; Garner, LC; Powell, K; Amini, A; Irwin, SL; Ferry, H; Ambrose, T; Friend, P; Vrakas, G; Reddy, S; Soilleux, E; Klenerman, P; Allan, PJ |
| Publisher Information: |
Cell Press |
| Publication Year: |
2021 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Tissue-resident memory T (T_RM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal T_RM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human T_RM cells through study of donor-derived T_RM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8+ T_RM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8+ T_RM phenotypes. CD8+ CD69+CD103+ T_RM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin+CD69+CD103− T_RM cells have higher granzyme expression. Analysis of intestinal CD4+ T cells identifies several parallels, including a β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ T_RM cells. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.celrep.2020.108661 |
| DOI: |
10.1016/j.celrep.2020.108661 |
| Availability: |
https://doi.org/10.1016/j.celrep.2020.108661; https://ora.ox.ac.uk/objects/uuid:512d8b7e-fb3c-4d7d-bcc2-691469e9356f |
| Rights: |
info:eu-repo/semantics/embargoedAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.DB270A4D |
| Database: |
BASE |