Files and links (1)
Published, Version of Record (VoR)CC BY-NC-ND V4.0, Restricted
Journal article
Developmentally distinct CD4+ Treg lineages shape the CD8+ T cell response to acute Listeria infection
Proceedings of the National Academy of Sciences - PNAS, v 119(10), pp 1-12
08 Mar 2022
PMID: 35239442
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
CD4+ regulatory T cells (Tregs) must prevent immunopathology by cytotoxic CD8+ T lymphocytes (CTLs) responding to acute infection and restore immune homeostasis following pathogen clearance, yet little is known about the specific populations or mechanisms governing these discrete events. We found that acute Listeria monocytogenes (L. monocytogenes) infection produces a phenotypically and functionally complex Treg response comprising two separate suppressor cell subpopulations, with an early Treg peak occurring at 24 h postinfection and a later peak arising by day 7. The first wave of Tregs suppress primary CTL expansion via a contact-independent mechanism involving CD73-derived adenosine (Ado) production from extracellular adenosine monophosphate (5′-AMP), while the second originates from different precursors and acts throughout the contraction phase via contact-dependent gap junction transfer of 3′,5′-cyclic adenosine monophosphate (cAMP)—both potent inhibitors of T cell proliferation. We speculate that the early activation of CD73 on Tregs is enhanced in inflamed tissues due to high purine release from apoptotic cells, whereas late-phase gap junction–dependent Tregs rely more on cell number and less on tissue inflammation. This study importantly reveals that CTL priming and contraction phases are separately fine-tuned by developmentally distinct Treg lineages during an acute infection.
Metrics
Details
- Title
- Developmentally distinct CD4+ Treg lineages shape the CD8+ T cell response to acute Listeria infection
- Creators
- Joseph S. Dolina - La Jolla Institute for ImmunologyJoey Lee - La Jolla Institute for ImmunologyEugene L. Moore - La Jolla Institute for ImmunologyJennifer L. Hope - Drexel University, Microbiology and ImmunologyDonald T. Gracias - Drexel UniversityTakaji Matsutani - Repertoire Genesis IncorporationAshu Chawla - La Jolla Institute for ImmunologyJason A. Greenbaum - La Jolla Institute for ImmunologyJoel Linden - La Jolla Institute for ImmunologyStephen P. Schoenberger - La Jolla Institute for Immunology
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 119(10), pp 1-12
- Publisher
- National Academy of Sciences
- Number of pages
- 12
- Grant note
- R01 AI107010 / HHS | National Institutes of Health (NIH) S10 RR027366 / HHS | National Institutes of Health (NIH) S10 OD016262 / HHS | National Institutes of Health (NIH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000771755000003
- Scopus ID
- 2-s2.0-85125687772
- Other Identifier
- 991021811915704721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Multidisciplinary Sciences