Abstract
Non-recirculating tissue-resident memory T cells (TRMs) are the predominant T cell subset in diverse tissue sites, where they mediate protective immune responses in situ. Here, we reveal a role for TRM in maintaining immune homeostasis in the human pancreas through interactions with resident macrophages and the PD-1/PD-L1 inhibitory pathway. Using tissues obtained from organ donors, we identify that pancreas T cells comprise CD8+PD-1hi TRMs, which are phenotypically, functionally, and transcriptionally distinct compared to TRMs in neighboring jejunum and lymph node sites. Pancreas TRMs cluster with resident macrophages throughout the exocrine areas; TRM effector functions are enhanced by macrophage-derived co-stimulation and attenuated by the PD-1/PD-L1 pathways. Conversely, in samples from chronic pancreatitis, TRMs exhibit reduced PD-1 expression and reduced interactions with macrophages. These findings suggest important roles for PD-1 and TRM-macrophage interactions in controlling tissue homeostasis and immune dysfunctions underlying inflammatory disease, with important implications for PD-1-based immunotherapies.
Original language | English (US) |
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Pages (from-to) | 3916-3932.e5 |
Journal | Cell Reports |
Volume | 29 |
Issue number | 12 |
DOIs | |
State | Published - Dec 17 2019 |
Externally published | Yes |
Keywords
- PD-1
- chronic pancreatitis
- macrophage
- memory T cells
- mucosal immunity
- pancreas
- tissue immunity
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology