ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

PD-1 Signals Murine and Human Treg for Enhanced Migration

W. Piao1, Y. Xiong1, L. Li1, K. Hippen2, Y. Zhang2, V. Saxena1, C. Paluskievicz1, M. WillsonShirkey1, B. Blazar3, L. Riella4, J. Bromberg5

1Surgery, U of Maryland, Baltimore, MD, 2U of Minnesota, Minneapolis, MN, 3Surgery, U of Minnesota, Minneapolis, MN, 4Harvard U, Boston, MA, 5Surgery and Microbiology and Immunology, U of Maryland, Baltimore, MD

Meeting: 2020 American Transplant Congress

Abstract number: D-348

Keywords: Endothelial cells, Immunosuppression, Nuclear factor-kappa B (NF-kB), T cells

Session Information

Session Name: Poster Session D: Lymphocyte Biology: Signaling, Co-Stimulation, Regulation

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: Programmed death-1 (PD-1) attenuates immune responses. Engagement of PD-1 by its ligands PD-L1 or PD-L2 regulates T cell development, proliferation, cytokine production, and apoptosis. However, little is known about PD-1 signaling or function in Treg. Since we showed that Treg express higher levels of surface PD-1 than naïve CD4 T cells, and since PD-L1 is highly expressed by lymphatic endothelial cells (LEC), we hypothesized that Treg-LEC PD-1/PD-L1 signaling regulates transendothelial migration and Treg function.

*Methods: Human Treg, naïve and activated CD4 T cells, and murine wild type and PD-1-/- Treg were isolated and migrated across human or mouse LEC in a transwell based in vitro assay. Anti-PD-1 and anti-PD-L1 mAbs and recombinant PD-1-Ig and PD-L1-Ig were used to block or stimulate PD-1 or PD-L1 on T cells and LEC. Their effects were assessed for signaling and migration.

*Results: Treg expressed higher levels of PD-1 than non-Treg CD4 T cells. Treg PD-1 expression was enhanced by migration across LEC. In contrast, PD-1 expression was not enhanced on other CD4 T cells that migrated across LEC or on Treg that migrated only across plastic membranes. Blockade of PD-1 by anti-PD-1 mAb on human or mouse Treg, but not non-Treg, inhibited lymphatic transendothelial migration in vitro and in vivo. Treg also expressed PD-L1, yet blockade of PD-L1 by anti-PD-L1 mAb on human or mouse Treg did not affect Treg migration. However, blocking PD-L1 on human or mouse LEC inhibited Treg but not non-Treg migration in vitro and in vivo. PD-1-/- Treg also had decreased transendothelial migration in vitro. PD-1-/- Treg had limited migration to local LNs in vivo compared to wild type. Immobilized PD-L1-Ig activated Treg PD-1 signaling and promoted Treg transendothelial migration. Immunoblotting showed crosslinking PD-1 on Treg triggered extracellular-signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs), as well as PI3K serine/threonine protein kinase Akt (Thr308) activation but inhibited classical NFκB (p-65) signaling on Treg.

*Conclusions: Treg PD-1 signals through MAPKs and PI3K/Akt pathways to maintain or increase surface PD-1 expression on Treg. Treg PD-1 interacts with its ligand PD-L1 on LEC to promote Treg transendothelial migration. PD-1 is required for the enhanced Treg migration in vitro and in vivo, demonstrating a unique and novel function for these molecules.

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

To cite this abstract in AMA style:

Piao W, Xiong Y, Li L, Hippen K, Zhang Y, Saxena V, Paluskievicz C, WillsonShirkey M, Blazar B, Riella L, Bromberg J. PD-1 Signals Murine and Human Treg for Enhanced Migration [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/pd-1-signals-murine-and-human-treg-for-enhanced-migration/. Accessed June 6, 2025.

« Back to 2020 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences