Tissue-Resident Memory T Cells Mediate Immune Homeostasis in the Human Pancreas through the PD-1/PD-L1 Pathway. Academic Article uri icon

Overview

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.

authors

  • Weisberg, Stuart P
  • Carpenter, Dustin
  • Chait, Michael
  • Dogra, Pranay
  • Gartrell-Corrado, Robyn D
  • Chen, Andrew X
  • Campbell, Sean
  • Liu, Wei
  • Saraf, Pooja
  • Snyder, Mark E
  • Kubota, Masaru
  • Danzl, Nichole M
  • Schrope, Beth A
  • Rabadan, Raul
  • Saenger, Yvonne
  • Chen, Xiaojuan
  • Farber, Donna L

publication date

  • December 17, 2019

Research

keywords

  • B7-H1 Antigen
  • Immunologic Memory
  • Pancreas
  • Pancreatitis
  • Programmed Cell Death 1 Receptor
  • T-Lymphocyte Subsets

Identity

PubMed Central ID

  • PMC6939378

Scopus Document Identifier

  • 85076370395

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2019.11.056

PubMed ID

  • 31851923

Additional Document Info

volume

  • 29

issue

  • 12